Is CSF1R p.Trp50Leu (c.149G>T) pathogenic?

CSF1R p.Trp50Leu (c.149G>T) is classified Likely benign in CSF1R (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-23). AlphaMissense: likely pathogenic (0.8209); Very rare (popmax 0.00133%, afr).

How common is CSF1R p.Trp50Leu (c.149G>T) in the general population?

CSF1R p.Trp50Leu (c.149G>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CSF1R p.Trp50Leu (c.149G>T)?

AlphaMissense predicts likely pathogenic (score 0.8209) — an in-silico prediction, not a clinical call.

CSF1R p.Trp50Leu

c.149G>T · rs1561940695 · VCV2726733

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8209 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8209	likely pathogenic
REVEL	0.543	indeterminate
SaProt	LLR -9.93	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 25 kb · p 0.12 · regional, not allelic
Overall
CADD	25.8	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 0.00133% African / African-American · 1/75,050 alleles

Overall 6.84e-05% 1/1,461,884 alleles · very rare

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: CSF1R
Protein: p.Trp50Leu
Coding: c.149G>T
MANE Select: NM_001288705
dbSNP: rs1561940695
Type: single nucleotide variant
Location: chr5:150080925 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 26 PDB
Residue 50: a disulfide bond; the ig-like c2-type 1 domain; a β-strand

Full CSF1R gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSF1R p.Ala780Val Likely pathogenic ★★ same type
CSF1R p.Ala781Val Pathogenic ★★ same type
CSF1R p.Arg676Ter Pathogenic ★★ same type
CSF1R p.Arg777Gln Pathogenic ★★ same type
CSF1R p.Arg777Trp Pathogenic/Likely pathogenic ★★ same type
CSF1R p.Arg782Cys Pathogenic/Likely pathogenic ★★ same type
CSF1R p.Arg782His Pathogenic/Likely pathogenic ★★ same type
CSF1R p.Gln481Ter Pathogenic ★★ 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/csf1r-p-trp50leu (accessed [today's date]).

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