Is GFAP p.Pro44Ala (c.130C>G) pathogenic?

GFAP p.Pro44Ala (c.130C>G) is classified Likely benign in GFAP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-07-30). AlphaMissense: likely benign (0.0521); Rare (popmax 0.121%, afr); Associated with Inborn genetic diseases.

What condition is associated with GFAP p.Pro44Ala (c.130C>G)?

GFAP p.Pro44Ala (c.130C>G) is associated with Inborn genetic diseases (ClinVar).

How common is GFAP p.Pro44Ala (c.130C>G) in the general population?

GFAP p.Pro44Ala (c.130C>G) is rare (popmax 0.121%, afr) (gnomAD).

What do computational predictors say about GFAP p.Pro44Ala (c.130C>G)?

AlphaMissense predicts likely benign (score 0.0521) — an in-silico prediction, not a clinical call.

GFAP p.Pro44Ala

c.130C>G · rs144543354 · VCV1673480

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0521 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.121%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0521	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -6.07	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 4.4	GERP -1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 177 bp · p 0.87 · regional, not allelic
Overall
CADD	15.81	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 0.121% African / African-American · 91/75,026 alleles

Filtering AF 0.101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0936%

Overall 0.00621% 100/1,611,506 alleles · rare exomes 48/1,459,146 · genomes 52/152,360 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.121%	824
Admixed American	0.00834%	11,998
Remaining individualsnot grpmax-eligible	0.00641%	15,595

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.Pro44Ala
Coding: c.130C>G
MANE Select: NM_002055
dbSNP: rs144543354
Type: single nucleotide variant
Location: chr17:44915357 (GRCh38)
Gene constraint: LOEUF 0.991 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.70 · 1 PDB
Residue 44: 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.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
GFAP p.Glu391Lys 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-pro44ala (accessed [today's date]).

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