Is GIT1 p.Ile347Val (c.1039A>G) pathogenic?

GIT1 p.Ile347Val (c.1039A>G) is classified Uncertain significance in GIT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-17). AlphaMissense: ambiguous (0.3728); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with GIT1 p.Ile347Val (c.1039A>G)?

GIT1 p.Ile347Val (c.1039A>G) is associated with Inborn genetic diseases (ClinVar).

How common is GIT1 p.Ile347Val (c.1039A>G) in the general population?

GIT1 p.Ile347Val (c.1039A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GIT1 p.Ile347Val (c.1039A>G)?

AlphaMissense predicts ambiguous (score 0.3728) — an in-silico prediction, not a clinical call.

GIT1 p.Ile347Val

c.1039A>G · rs2033240901 · VCV2518103

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3728 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3728	ambiguous
REVEL	0.182	moderately benign-leaning
SaProt	LLR -7.34	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 1,519 bp · p 0.045 · regional, not allelic
Overall
CADD	24.5	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: GIT1
Protein: p.Ile347Val
Coding: c.1039A>G
MANE Select: NM_014030
dbSNP: rs2033240901
Type: single nucleotide variant
Location: chr17:29577190 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.72
Residue 347: the 'interaction with pclo' region; the 'interaction with ptk2/fak1' region; the 'interaction with arhgef7' region

Full GIT1 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

GIT1 c.762-205C>T Uncertain significance ★ same condition
GIT1 p.Ala130Thr Uncertain significance ★ ⚠ same condition
GIT1 p.Ala183Gly Uncertain significance ★ same condition
GIT1 p.Ala311Val Uncertain significance ★ ⚠ same condition
GIT1 p.Ala402Thr Uncertain significance ★ ⚠ same condition
GIT1 p.Ala466Val Uncertain significance ★ ⚠ same condition
GIT1 p.Ala488Thr Uncertain significance ★ ⚠ same condition
GIT1 p.Ala488Val 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/git1-p-ile347val (accessed [today's date]).

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