Is CSF1R p.Val268Ile (c.802G>A) pathogenic?

CSF1R p.Val268Ile (c.802G>A) is classified Benign/Likely benign in CSF1R (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-14). AlphaMissense: likely benign (0.1884); Rare (popmax 0.314%, afr); Associated with leukoencephalopathy, hereditary diffuse, with spheroids.

What condition is associated with CSF1R p.Val268Ile (c.802G>A)?

CSF1R p.Val268Ile (c.802G>A) is associated with leukoencephalopathy, hereditary diffuse, with spheroids, CSF1R-related disorder (ClinVar).

How common is CSF1R p.Val268Ile (c.802G>A) in the general population?

CSF1R p.Val268Ile (c.802G>A) is rare (popmax 0.314%, afr) (gnomAD).

What do computational predictors say about CSF1R p.Val268Ile (c.802G>A)?

AlphaMissense predicts likely benign (score 0.1884) — an in-silico prediction, not a clinical call.

CSF1R p.Val268Ile

c.802G>A · rs143274491 · VCV352161

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1884 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.314%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

leukoencephalopathy, hereditary diffuse, with spheroids

Computational evidence

Protein change
AlphaMissense	0.1884	likely benign
REVEL	0.185	benign-leaning
SaProt	LLR -8.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.25	acceptor gain · deltas
Pangolin	Δ0.30	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.6	GERP 1.9, phastCons 0.93
Regional constraint	o/e 0.94	unconstrained · MANE · 25 kb · p 0.12 · regional, not allelic
Overall
CADD	21.0	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 0.314% African / African-American · 236/75,042 alleles

Filtering AF 0.281% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.269%

Overall 0.0201% 325/1,614,188 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.314%	318
Ashkenazi Jewishnot grpmax-eligible	0.182%	548
Remaining individualsnot grpmax-eligible	0.04%	2,500
Admixed American	0.00667%	15,003
South Asian	0.0011%	91,076
European (non-Finnish)	0.000424%	236,007

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.Val268Ile
Coding: c.802G>A
MANE Select: NM_001288705
dbSNP: rs143274491
Type: single nucleotide variant
Location: chr5:150077363 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 26 PDB
Residue 268: a disulfide bond; the ig-like c2-type 3 domain

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

Disease context

leukoencephalopathy, hereditary diffuse, with spheroids — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: CSF1R-related disorder

Similar variants

CSF1R p.Ala781Val Pathogenic ★★ same condition
CSF1R p.Arg777Gln Pathogenic ★★ same condition
CSF1R p.Arg777Trp Pathogenic/Likely pathogenic ★★ same condition
CSF1R p.Arg782Cys Pathogenic/Likely pathogenic ★★ same condition
CSF1R p.Arg782His Pathogenic/Likely pathogenic ★★ same condition
CSF1R p.Gln481Ter Pathogenic ★★ same condition
CSF1R p.Gln642Ter Pathogenic/Likely pathogenic ★★ same condition
CSF1R p.Gln877Ter Likely pathogenic ★★ same condition

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-val268ile (accessed [today's date]).

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