Is GFAP p.Ala26Val (c.77C>T) pathogenic?

GFAP p.Ala26Val (c.77C>T) is classified Conflicting classifications of pathogenicity in GFAP (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-02-26). AlphaMissense: likely benign (0.0692); Rare (popmax 0.152%, mid); Associated with Inborn genetic diseases.

What condition is associated with GFAP p.Ala26Val (c.77C>T)?

GFAP p.Ala26Val (c.77C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GFAP p.Ala26Val (c.77C>T) in the general population?

GFAP p.Ala26Val (c.77C>T) is rare (popmax 0.152%, mid) (gnomAD).

What do computational predictors say about GFAP p.Ala26Val (c.77C>T)?

AlphaMissense predicts likely benign (score 0.0692) — an in-silico prediction, not a clinical call.

GFAP p.Ala26Val

c.77C>T · rs139837765 · VCV1485530

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0692 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.152%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0692	likely benign
REVEL	0.218	benign-leaning
SaProt	LLR -7.52	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 0.7	GERP -3.4, phastCons 0.001
Regional constraint	o/e 1.02	unconstrained · MANE · 177 bp · p 0.87 · regional, not allelic
Overall
CADD	7.031	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 0.152% Middle Eastern · 9/5,908 alleles

Filtering AF 0.0794% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0593%

Overall 0.00554% 89/1,607,308 alleles · rare exomes 78/1,455,142 · genomes 11/152,166 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.152%	656
Admixed American	0.0101%	9,948
European (non-Finnish)	0.00595%	16,806
Remaining individualsnot grpmax-eligible	0.00322%	31,052
African / African-American	0.00134%	74,842
South Asian	0.0011%	90,582

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: GFAP
Protein: p.Ala26Val
Coding: c.77C>T
MANE Select: NM_002055
dbSNP: rs139837765
Type: single nucleotide variant
Location: chr17:44915410 (GRCh38)
Gene constraint: LOEUF 0.991 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.70 · 1 PDB
Residue 26: the 'head' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GFAP p.Ala26Thr Likely benign ★ same residue
GFAP p.Ala246Val Uncertain significance ★★ ⚠ same condition
GFAP p.Arg12Gly Uncertain significance ★★ ⚠ same condition
GFAP p.Arg136Trp Uncertain significance ★★ ⚠ same condition
GFAP p.Arg29Cys Uncertain significance ★★ ⚠ same condition
GFAP p.Arg5Cys Uncertain significance ★★ ⚠ same condition
GFAP p.Asp266Glu Uncertain significance ★★ ⚠ same condition
GFAP p.Glu273Asp Uncertain significance ★★ ⚠ 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/gfap-p-ala26val (accessed [today's date]).

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