Is CSF1 p.Ala531Val (c.1592C>T) pathogenic?

CSF1 p.Ala531Val (c.1592C>T) is classified Likely benign in CSF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-16). AlphaMissense: likely benign (0.0622); Rare (popmax 0.139%, afr).

How common is CSF1 p.Ala531Val (c.1592C>T) in the general population?

CSF1 p.Ala531Val (c.1592C>T) is rare (popmax 0.139%, afr) (gnomAD).

What do computational predictors say about CSF1 p.Ala531Val (c.1592C>T)?

AlphaMissense predicts likely benign (score 0.0622) — an in-silico prediction, not a clinical call.

CSF1 p.Ala531Val

c.1592C>T · rs2229167 · VCV745764

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0622 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.139%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0622	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -7.11	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 -0.29	GERP -3.2
Regional constraint	o/e 1.00	unconstrained · MANE · 7,862 bp · p 0.92 · regional, not allelic
Overall
CADD	0.145	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 0.139% African / African-American · 104/74,692 alleles

Filtering AF 0.118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.109%

Overall 0.0192% 307/1,601,696 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.139%	718
East Asian	0.0429%	2,331
Remaining individualsnot grpmax-eligible	0.0306%	3,264
Admixed American	0.0206%	4,864
Middle Eastern	0.0165%	6,048
European (non-Finnish)	0.0123%	8,153
Finnishnot grpmax-eligible	0.0079%	12,661
South Asian	0.00338%	29,573

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.Ala531Val
Coding: c.1592C>T
MANE Select: NM_000757
dbSNP: rs2229167
Type: single nucleotide variant
Location: chr1:109924798 (GRCh38)
Gene constraint: LOEUF 0.338 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 58.62 · 8 PDB
Residue 531: a UniProt-annotated variant site (in); 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-ala531val (accessed [today's date]).

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