Is GFAP p.Arg88Ser (c.262C>A) pathogenic?

GFAP p.Arg88Ser (c.262C>A) is classified Pathogenic in GFAP (ClinVar, No assertion criteria, 3 submitters; last evaluated 2001-11-01). AlphaMissense: likely pathogenic (0.9672); Absent from gnomAD v4.1; Associated with Alexander disease.

What condition is associated with GFAP p.Arg88Ser (c.262C>A)?

GFAP p.Arg88Ser (c.262C>A) is associated with Alexander disease (ClinVar).

How common is GFAP p.Arg88Ser (c.262C>A) in the general population?

GFAP p.Arg88Ser (c.262C>A) is absent from gnomAD v4.1 (gnomAD).

How is Alexander disease inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about GFAP p.Arg88Ser (c.262C>A)?

AlphaMissense predicts likely pathogenic (score 0.9672) — an in-silico prediction, not a clinical call.

GFAP p.Arg88Ser

c.262C>A · rs61622935 · VCV16173

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9672 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Alexander disease

Computational evidence

Protein change
AlphaMissense	0.9672	likely pathogenic ✓ concordant with ClinVar · top 7% in GFAP
REVEL	0.932	strongly pathogenic-leaning
SaProt	LLR -13.29	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.26	constrained · MANE · 95 bp · p 5.1e-07 · regional, not allelic
Overall
CADD	34.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GFAP
Protein: p.Arg88Ser
Coding: c.262C>A
MANE Select: NM_002055
dbSNP: rs61622935
Type: single nucleotide variant
Location: chr17:44915225 (GRCh38)
Gene constraint: LOEUF 0.991 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.70 · 1 PDB
Residue 88: the if rod domain; the 'coil 1a' region; a UniProt-annotated variant site (in alxdrd)

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

Disease context

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

For Alexander disease (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages
Prevalence: <1 / 1 000 000 (Japan)

Similar variants

GFAP p.Arg88Cys Pathogenic ★★ same residue
GFAP p.Arg88= Likely benign ★ same residue
GFAP p.Arg239Cys Pathogenic ★★ same condition
GFAP p.Arg239His Pathogenic ★★ same condition
GFAP p.Arg239Leu Pathogenic ★★ same condition
GFAP p.Arg258Cys Pathogenic ★★ ⚠ same condition
GFAP p.Arg376Trp Pathogenic ★★ same condition
GFAP p.Arg416Trp 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/gfap-p-arg88ser (accessed [today's date]).

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