Is GIT1 p.Pro533Leu (c.1598C>T) pathogenic?

GIT1 p.Pro533Leu (c.1598C>T) is classified Uncertain significance in GIT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-20). AlphaMissense: likely benign (0.315); Very rare (popmax 0.005%, amr); Associated with Inborn genetic diseases.

What condition is associated with GIT1 p.Pro533Leu (c.1598C>T)?

GIT1 p.Pro533Leu (c.1598C>T) is associated with Inborn genetic diseases (ClinVar).

How common is GIT1 p.Pro533Leu (c.1598C>T) in the general population?

GIT1 p.Pro533Leu (c.1598C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about GIT1 p.Pro533Leu (c.1598C>T)?

AlphaMissense predicts likely benign (score 0.315) — an in-silico prediction, not a clinical call.

GIT1 p.Pro533Leu

c.1598C>T · VCV3520239

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.315 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.315	likely benign
REVEL	0.75	pathogenic-leaning
SaProt	LLR -7.15	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 1,519 bp · p 0.045 · regional, not allelic
Overall
CADD	24.6	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 0.005% Admixed American · 3/59,948 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000187% 3/1,608,092 alleles · very rare exomes 3/1,455,752 · genomes 0/152,340 · 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.Pro533Leu
Coding: c.1598C>T
MANE Select: NM_014030
Type: single nucleotide variant
Location: chr17:29576233 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.72
Residue 533: the 'interaction with nck2 and grin3a' region; the 'required for localization at synapses' region; the 'interaction with ikbkg' 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-pro533leu (accessed [today's date]).

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