Is GIT1 p.Tyr710Cys (c.2129A>G) pathogenic?

GIT1 p.Tyr710Cys (c.2129A>G) is classified Uncertain significance in GIT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-29). AlphaMissense: likely benign (0.1005); Ultra-rare (popmax 0.0203%, eas); Associated with Inborn genetic diseases.

What condition is associated with GIT1 p.Tyr710Cys (c.2129A>G)?

GIT1 p.Tyr710Cys (c.2129A>G) is associated with Inborn genetic diseases (ClinVar).

How common is GIT1 p.Tyr710Cys (c.2129A>G) in the general population?

GIT1 p.Tyr710Cys (c.2129A>G) is ultra-rare (popmax 0.0203%, eas) (gnomAD).

What do computational predictors say about GIT1 p.Tyr710Cys (c.2129A>G)?

AlphaMissense predicts likely benign (score 0.1005) — an in-silico prediction, not a clinical call.

GIT1 p.Tyr710Cys

c.2129A>G · rs375882746 · VCV3099912

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1005 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0203%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1005	likely benign
REVEL	0.343	indeterminate
SaProt	LLR -6.41	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.1	GERP 1.8, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 995 bp · p 1.9e-09 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0203% East Asian · 9/44,386 alleles

Filtering AF 0.0105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00787%

Overall 0.000751% 12/1,596,850 alleles · ultra-rare exomes 12/1,444,612 · genomes 0/152,238 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0203%	4,932
Remaining individualsnot grpmax-eligible	0.00323%	31,006
European (non-Finnish)	8.52e-05%	1,174,220

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.Tyr710Cys
Coding: c.2129A>G
MANE Select: NM_014030
dbSNP: rs375882746
Type: single nucleotide variant
Location: chr17:29574859 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.72
Residue 710: the 'interaction with pxn and tgfb1i1' 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-tyr710cys (accessed [today's date]).

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