Is CSF2RB p.Ala645= (c.1935G>A) pathogenic?

CSF2RB p.Ala645= (c.1935G>A) is classified Likely benign in CSF2RB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). Very rare (popmax 0.00615%, nfe).

How common is CSF2RB p.Ala645= (c.1935G>A) in the general population?

CSF2RB p.Ala645= (c.1935G>A) is very rare (popmax 0.00615%, nfe) (gnomAD).

CSF2RB p.Ala645=

c.1935G>A · rs372368037 · VCV1665313

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00615%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.045	GERP -2.5
Overall
CADD	3.934	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00615% European (non-Finnish) · 71/1,154,698 alleles

Filtering AF 0.00497% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00456%

Overall 0.00485% 76/1,565,632 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00615%	16,263
East Asian	0.00236%	42,364
Finnishnot grpmax-eligible	0.00166%	60,300
Remaining individualsnot grpmax-eligible	0.00165%	60,668
African / African-American	0.00135%	73,998
South Asian	0.00116%	86,034

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.Ala645=
Coding: c.1935G>A
MANE Select: NM_000395
dbSNP: rs372368037
Type: single nucleotide variant
Location: chr22:36937743 (GRCh38)
Gene constraint: LOEUF 0.511 · pLI 0.93 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.50 · 10 PDB

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

Similar variants

CSF2RB p.Ala645Val Uncertain significance ★ ⚠ same residue
CSF2RB p.Ala185Thr Uncertain significance ★★ ⚠ same type
CSF2RB p.Ala255Thr Uncertain significance ★★ ⚠ same type
CSF2RB p.Ala314Thr Uncertain significance ★★ ⚠ same type
CSF2RB p.Ala314Val Uncertain significance ★★ ⚠ same type
CSF2RB p.Ala394Thr Uncertain significance ★★ ⚠ same type
CSF2RB p.Ala455Thr Uncertain significance ★★ ⚠ same type
CSF2RB p.Ala576Thr Uncertain significance ★★ ⚠ same type

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-ala645 (accessed [today's date]).

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