Is GFAP p.Ser38Phe (c.113C>T) pathogenic?

GFAP p.Ser38Phe (c.113C>T) is classified Uncertain significance in GFAP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-15). AlphaMissense: likely benign (0.1589); Very rare (popmax 0.00238%, nfe).

How common is GFAP p.Ser38Phe (c.113C>T) in the general population?

GFAP p.Ser38Phe (c.113C>T) is very rare (popmax 0.00238%, nfe) (gnomAD).

What do computational predictors say about GFAP p.Ser38Phe (c.113C>T)?

AlphaMissense predicts likely benign (score 0.1589) — an in-silico prediction, not a clinical call.

GFAP p.Ser38Phe

c.113C>T · rs1455211354 · VCV1466016

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1589 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00238%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1589	likely benign
REVEL	0.421	indeterminate
SaProt	LLR -11.32	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.6	GERP 0.75, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 177 bp · p 0.87 · regional, not allelic
Overall
CADD	23.6	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 0.00238% European (non-Finnish) · 28/1,176,888 alleles

Filtering AF 0.00165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.0018% 29/1,609,252 alleles · very rare exomes 27/1,457,048 · genomes 2/152,204 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00238%	42,032
African / African-American	0.00134%	74,866

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.Ser38Phe
Coding: c.113C>T
MANE Select: NM_002055
dbSNP: rs1455211354
Type: single nucleotide variant
Location: chr17:44915374 (GRCh38)
Gene constraint: LOEUF 0.991 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.70 · 1 PDB
Residue 38: a modified residue (phosphoserine; by aurkb and rock1); the 'head' region

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

Similar variants

GFAP p.Arg239Cys Pathogenic ★★ same type
GFAP p.Arg239His Pathogenic ★★ same type
GFAP p.Arg239Leu Pathogenic ★★ same type
GFAP p.Arg258Cys Pathogenic ★★ ⚠ same type
GFAP p.Arg376Trp Pathogenic ★★ same type
GFAP p.Arg416Trp Pathogenic ★★ same type
GFAP p.Arg70Trp Pathogenic ★★ same type
GFAP p.Arg79Cys 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/gfap-p-ser38phe (accessed [today's date]).

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