Is GIT1 p.Pro17Arg (c.50C>G) pathogenic?

GIT1 p.Pro17Arg (c.50C>G) is classified Uncertain significance in GIT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-23). AlphaMissense: ambiguous (0.3991); Very rare (popmax 0.000115%, nfe); Associated with Inborn genetic diseases.

What condition is associated with GIT1 p.Pro17Arg (c.50C>G)?

GIT1 p.Pro17Arg (c.50C>G) is associated with Inborn genetic diseases (ClinVar).

How common is GIT1 p.Pro17Arg (c.50C>G) in the general population?

GIT1 p.Pro17Arg (c.50C>G) is very rare (popmax 0.000115%, nfe) (gnomAD).

What do computational predictors say about GIT1 p.Pro17Arg (c.50C>G)?

AlphaMissense predicts ambiguous (score 0.3991) — an in-silico prediction, not a clinical call.

GIT1 p.Pro17Arg

c.50C>G · VCV4263807

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3991 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000115%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3991	ambiguous
REVEL	0.142	moderately benign-leaning
SaProt	LLR -7.07	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 6.8	GERP 0.61, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 12 kb · p 1.9e-17 · 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

Grpmax group 0.000115% European (non-Finnish) · 1/870,176 alleles

Overall 9.5e-05% 1/1,053,180 alleles · very rare exomes 1/905,626 · genomes 0/147,554 · 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.Pro17Arg
Coding: c.50C>G
MANE Select: NM_014030
Type: single nucleotide variant
Location: chr17:29589329 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.72
Residue 17: 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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GIT1 p.Pro17Leu Uncertain significance ★ ⚠ same residue
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

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-pro17arg (accessed [today's date]).

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