Is GFAP p.Arg124= (c.370C>A) pathogenic?

GFAP p.Arg124= (c.370C>A) is classified Likely benign in GFAP (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-26). Very rare (popmax 0.000593%, nfe).

How common is GFAP p.Arg124= (c.370C>A) in the general population?

GFAP p.Arg124= (c.370C>A) is very rare (popmax 0.000593%, nfe) (gnomAD).

GFAP p.Arg124=

c.370C>A · rs780877810 · VCV722854

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.8	GERP 0.8, phastCons 0.83
Overall
CADD	5.092	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000593% European (non-Finnish) · 7/1,180,016 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,613,770 alleles · very rare exomes 6/1,461,590 · genomes 1/152,180 · joint denominator

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.Arg124=
Coding: c.370C>A
MANE Select: NM_002055
dbSNP: rs780877810
Type: single nucleotide variant
Location: chr17:44915117 (GRCh38)
Gene constraint: LOEUF 0.991 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.70 · 1 PDB
Residue 124: the if rod domain; an α-helix; the 'coil 1b' region

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

Similar variants

GFAP p.Arg124Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
GFAP p.Arg124Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
GFAP p.Arg124_Leu125insGluLeuArg Uncertain significance ★★ same residue
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

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-arg124 (accessed [today's date]).

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