Is CSF1R p.Asp269Glu (c.807T>A) pathogenic?

CSF1R p.Asp269Glu (c.807T>A) is classified Likely benign in CSF1R (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-17). AlphaMissense: likely benign (0.1811); Ultra-rare (popmax 0.0154%, sas).

How common is CSF1R p.Asp269Glu (c.807T>A) in the general population?

CSF1R p.Asp269Glu (c.807T>A) is ultra-rare (popmax 0.0154%, sas) (gnomAD).

What do computational predictors say about CSF1R p.Asp269Glu (c.807T>A)?

AlphaMissense predicts likely benign (score 0.1811) — an in-silico prediction, not a clinical call.

CSF1R p.Asp269Glu

c.807T>A · rs937043276 · VCV1414638

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1811 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0154%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1811	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -7.00	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 4.1	GERP 0.86, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 25 kb · p 0.12 · regional, not allelic
Overall
CADD	12.72	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 0.0154% South Asian · 14/91,086 alleles

Filtering AF 0.00919% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00735%

Overall 0.00229% 37/1,614,210 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0154%	6,506
Remaining individualsnot grpmax-eligible	0.0048%	20,837
European (non-Finnish)	0.00169%	59,002

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.Asp269Glu
Coding: c.807T>A
MANE Select: NM_001288705
dbSNP: rs937043276
Type: single nucleotide variant
Location: chr5:150077358 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 26 PDB
Residue 269: a disulfide bond; the ig-like c2-type 3 domain

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

Similar variants

CSF1R p.Asp269Tyr Uncertain significance ★ ⚠ 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
CSF1R p.Arg782His 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-asp269glu (accessed [today's date]).

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