Is GAB1 p.Pro17Ser (c.49C>T) pathogenic?

GAB1 p.Pro17Ser (c.49C>T) is classified Uncertain significance in GAB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-16). AlphaMissense: likely pathogenic (0.9992); Very rare (popmax 0.00182%, amr).

How common is GAB1 p.Pro17Ser (c.49C>T) in the general population?

GAB1 p.Pro17Ser (c.49C>T) is very rare (popmax 0.00182%, amr) (gnomAD).

What do computational predictors say about GAB1 p.Pro17Ser (c.49C>T)?

AlphaMissense predicts likely pathogenic (score 0.9992) — an in-silico prediction, not a clinical call.

GAB1 p.Pro17Ser

c.49C>T · VCV3852399

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9992 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00182%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9992	likely pathogenic · top 3% in GAB1
REVEL	0.14	moderately benign-leaning
SaProt	LLR -13.35	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 2.3, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 70 bp · p 0.45 · regional, not allelic
Overall
CADD	28.1	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 0.00182% Admixed American · 1/54,920 alleles

Overall 6.31e-05% 1/1,583,988 alleles · very rare exomes 0/1,431,800 · genomes 1/152,188 · 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: GAB1
Protein: p.Pro17Ser
Coding: c.49C>T
MANE Select: NM_002039
Type: single nucleotide variant
Location: chr4:143337237 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 53.30 · 5 PDB
Residue 17: the ph domain

Full GAB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GAB1 p.Pro17= Benign same residue
GAB1 c.1196-47G>A Benign ★★ same type
GAB1 c.1586-139G>A Benign ★★ same type
GAB1 c.1680-116A>G Benign ★★ same type
GAB1 c.1680-54A>G Benign ★★ same type
GAB1 p.Gly116Glu Pathogenic ★ same type
GAB1 c.1586-1631G>A Uncertain significance ★ same type
GAB1 c.1586-1660G>T Uncertain significance ★ 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/gab1-p-pro17ser (accessed [today's date]).

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