Is CSF2RB p.Ser625Phe (c.1874C>T) pathogenic?

CSF2RB p.Ser625Phe (c.1874C>T) is classified Conflicting classifications of pathogenicity in CSF2RB (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-07-10). AlphaMissense: likely benign (0.1182); Rare (popmax 0.18%, sas); Associated with surfactant metabolism dysfunction, pulmonary, 5.

What condition is associated with CSF2RB p.Ser625Phe (c.1874C>T)?

CSF2RB p.Ser625Phe (c.1874C>T) is associated with surfactant metabolism dysfunction, pulmonary, 5 (ClinVar).

How common is CSF2RB p.Ser625Phe (c.1874C>T) in the general population?

CSF2RB p.Ser625Phe (c.1874C>T) is rare (popmax 0.18%, sas) (gnomAD).

How is Hereditary pulmonary alveolar proteinosis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CSF2RB p.Ser625Phe (c.1874C>T)?

AlphaMissense predicts likely benign (score 0.1182) — an in-silico prediction, not a clinical call.

CSF2RB p.Ser625Phe

c.1874C>T · rs560156832 · VCV796279

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1182 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.18%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

surfactant metabolism dysfunction, pulmonary, 5

Computational evidence

Protein change
AlphaMissense	0.1182	likely benign
REVEL	0.383	indeterminate
SaProt	LLR -7.60	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.7	GERP 0.43, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 1,937 bp · p 0.11 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.18% South Asian · 153/84,812 alleles

Filtering AF 0.157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.148%

Overall 0.0127% 197/1,554,406 alleles · rare exomes 186/1,402,112 · genomes 11/152,294 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.18%	554
Remaining individualsnot grpmax-eligible	0.015%	6,686
Finnishnot grpmax-eligible	0.00337%	29,699
European (non-Finnish)	0.0027%	37,057
East Asian	0.00243%	41,162
African / African-American	0.00136%	73,328

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CSF2RB
Protein: p.Ser625Phe
Coding: c.1874C>T
MANE Select: NM_000395
dbSNP: rs560156832
Type: single nucleotide variant
Location: chr22:36937682 (GRCh38)
Gene constraint: LOEUF 0.511 · pLI 0.93 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.50 · 10 PDB
Residue 625: the 'disordered' region

Full CSF2RB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

surfactant metabolism dysfunction, pulmonary, 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary pulmonary alveolar proteinosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Elderly, Infancy
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

CSF2RB p.Arg211Gln Uncertain significance ★★ ⚠ same condition
CSF2RB p.Arg461Cys Uncertain significance ★★ ⚠ same condition
CSF2RB p.Glu533Lys Uncertain significance ★★ ⚠ same condition
CSF2RB p.Gly845Ser Uncertain significance ★★ ⚠ same condition
CSF2RB p.Thr196Asn Uncertain significance ★★ ⚠ same condition
CSF2RB p.Thr50Ile Uncertain significance ★★ ⚠ same condition
CSF2RB p.Arg215His Benign/Likely benign ★★ same condition
CSF2RB p.Ala749Pro Uncertain significance ★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/csf2rb-p-ser625phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown