Is GIT1 p.Met1Ile (c.3G>A) pathogenic?

GIT1 p.Met1Ile (c.3G>A) is classified Uncertain significance in GIT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-20). Very rare (popmax 0.000114%, nfe).

How common is GIT1 p.Met1Ile (c.3G>A) in the general population?

GIT1 p.Met1Ile (c.3G>A) is very rare (popmax 0.000114%, nfe) (gnomAD).

GIT1 p.Met1Ile

c.3G>A · VCV4934414

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000114%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function in a LoF-intolerant gene
REVEL	0.647	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP -0.38, phastCons 1
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000114% European (non-Finnish) · 1/878,684 alleles

Overall 9.29e-05% 1/1,076,052 alleles · very rare exomes 1/928,904 · genomes 0/147,148 · 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: GIT1
Protein: p.Met1Ile
Coding: c.3G>A
MANE Select: NM_014030
Type: single nucleotide variant
Location: chr17:29589376 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.72
Residue 1: the arf-gap domain; the 'interaction with gamma-tubulin and localization to the centrosome' region

Full GIT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GIT1 p.Pro83= Benign ★★ same type
GIT1 c.762-205C>T Uncertain significance ★ same type
GIT1 p.Ala130Thr Uncertain significance ★ ⚠ same type
GIT1 p.Ala183Gly Uncertain significance ★ same type
GIT1 p.Ala311Val Uncertain significance ★ ⚠ same type
GIT1 p.Ala402Thr Uncertain significance ★ ⚠ same type
GIT1 p.Ala466Val Uncertain significance ★ ⚠ same type
GIT1 p.Ala488Thr 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/git1-p-met1ile (accessed [today's date]).

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