Is CSF1R p.Pro132Ala (c.394C>G) pathogenic?

CSF1R p.Pro132Ala (c.394C>G) is classified Likely benign in CSF1R (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-08). AlphaMissense: likely benign (0.3347); Very rare (popmax 0.00668%, eas).

How common is CSF1R p.Pro132Ala (c.394C>G) in the general population?

CSF1R p.Pro132Ala (c.394C>G) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about CSF1R p.Pro132Ala (c.394C>G)?

AlphaMissense predicts likely benign (score 0.3347) — an in-silico prediction, not a clinical call.

CSF1R p.Pro132Ala

c.394C>G · rs769905192 · VCV2871705

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3347 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3347	likely benign
REVEL	0.513	indeterminate
SaProt	LLR -9.21	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 25 kb · p 0.12 · regional, not allelic
Overall
CADD	24.6	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 0.00668% East Asian · 3/44,898 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000186% 3/1,613,858 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.Pro132Ala
Coding: c.394C>G
MANE Select: NM_001288705
dbSNP: rs769905192
Type: single nucleotide variant
Location: chr5:150080250 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 26 PDB
Residue 132: an α-helix; a disulfide bond; a UniProt-annotated variant site (in banddos; impairs phosphorylation of jnk kinases upon stimulation with csf1); the ig-like c2-type 2 domain

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

Similar variants

CSF1R p.Pro132Leu Uncertain significance ★ ⚠ same residue
CSF1R p.Pro132= Likely benign ★ same residue
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

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-pro132ala (accessed [today's date]).

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