Is CSF1R p.Ala770Val (c.2309C>T) pathogenic?

CSF1R p.Ala770Val (c.2309C>T) is classified Uncertain significance in CSF1R (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-11). AlphaMissense: ambiguous (0.3928); Ultra-rare (popmax 0.0186%, mid); Associated with cerebral arterial disease.

What condition is associated with CSF1R p.Ala770Val (c.2309C>T)?

CSF1R p.Ala770Val (c.2309C>T) is associated with cerebral arterial disease (ClinVar).

How common is CSF1R p.Ala770Val (c.2309C>T) in the general population?

CSF1R p.Ala770Val (c.2309C>T) is ultra-rare (popmax 0.0186%, mid) (gnomAD).

What do computational predictors say about CSF1R p.Ala770Val (c.2309C>T)?

AlphaMissense predicts ambiguous (score 0.3928) — an in-silico prediction, not a clinical call.

CSF1R p.Ala770Val

c.2309C>T · VCV4075136

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3928 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0186%, mid)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

cerebral arterial disease

Computational evidence

Protein change
AlphaMissense	0.3928	ambiguous
REVEL	0.819	moderately pathogenic-leaning
SaProt	LLR -9.36	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.39	unconstrained · MANE · 2,952 bp · p 1.2e-16 · regional, not allelic
Overall
CADD	31.0	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 0.0186% Middle Eastern · 1/5,388 alleles

Filtering AF 0.00291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0026%

Overall 0.00291% 47/1,613,040 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0186%	5,388
European (non-Finnish)	0.00381%	26,220
Remaining individualsnot grpmax-eligible	0.0016%	62,396

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.Ala770Val
Coding: c.2309C>T
MANE Select: NM_001288705
Type: single nucleotide variant
Location: chr5:150057297 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 26 PDB
Residue 770: the protein kinase domain; an α-helix; a UniProt-annotated variant site (in banddos); a UniProt-annotated variant site (in hdls1)

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

Disease context

cerebral arterial disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CSF1R p.Ala770Thr Uncertain significance ★★ ⚠ same residue
CSF1R p.Ala770Pro Pathogenic ★ 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-ala770val (accessed [today's date]).

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