Is CSF1 p.Val550Ala (c.1649T>C) pathogenic?

CSF1 p.Val550Ala (c.1649T>C) is classified Uncertain significance in CSF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: likely benign (0.1471); Ultra-rare (popmax 0.07%, amr).

How common is CSF1 p.Val550Ala (c.1649T>C) in the general population?

CSF1 p.Val550Ala (c.1649T>C) is ultra-rare (popmax 0.07%, amr) (gnomAD).

What do computational predictors say about CSF1 p.Val550Ala (c.1649T>C)?

AlphaMissense predicts likely benign (score 0.1471) — an in-silico prediction, not a clinical call.

CSF1 p.Val550Ala

c.1649T>C · VCV4234795

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1471 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.07%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1471	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -6.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP 0.59, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 7,862 bp · p 0.92 · regional, not allelic
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.07% Admixed American · 42/59,992 alleles

Filtering AF 0.0532% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0473%

Overall 0.00266% 43/1,613,856 alleles · ultra-rare exomes 39/1,461,764 · genomes 4/152,092 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.07%	1,428
Remaining individualsnot grpmax-eligible	0.0016%	62,478

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: CSF1
Protein: p.Val550Ala
Coding: c.1649T>C
MANE Select: NM_000757
Type: single nucleotide variant
Location: chr1:109925173 (GRCh38)
Gene constraint: LOEUF 0.338 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 58.62 · 8 PDB
Residue 550: the 'disordered' region

Full CSF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSF1 p.Ala511= Benign ★★ same type
CSF1 p.Glu292= Benign ★★ same type
CSF1 p.Ala286Asp Uncertain significance ★ ⚠ same type
CSF1 p.Ala3Thr Uncertain significance ★ ⚠ same type
CSF1 p.Ala460Glu Uncertain significance ★ ⚠ same type
CSF1 p.Arg252Trp Uncertain significance ★ ⚠ same type
CSF1 p.Arg374Met Uncertain significance ★ ⚠ same type
CSF1 p.Arg449Gln 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/csf1-p-val550ala (accessed [today's date]).

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