Is GIT1 p.Leu186Val (c.556C>G) pathogenic?

GIT1 p.Leu186Val (c.556C>G) is classified Uncertain significance in GIT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-18). AlphaMissense: likely pathogenic (0.9195); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with GIT1 p.Leu186Val (c.556C>G)?

GIT1 p.Leu186Val (c.556C>G) is associated with Inborn genetic diseases (ClinVar).

How common is GIT1 p.Leu186Val (c.556C>G) in the general population?

GIT1 p.Leu186Val (c.556C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GIT1 p.Leu186Val (c.556C>G)?

AlphaMissense predicts likely pathogenic (score 0.9195) — an in-silico prediction, not a clinical call.

GIT1 p.Leu186Val

c.556C>G · rs2508547275 · VCV2272010

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9195 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9195	likely pathogenic
REVEL	0.752	pathogenic-leaning
SaProt	LLR -12.71	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP -0.08, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 12 kb · p 1.9e-17 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Leu186Val
Coding: c.556C>G
MANE Select: NM_014030
dbSNP: rs2508547275
Type: single nucleotide variant
Location: chr17:29581994 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.72

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-leu186val (accessed [today's date]).

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