Is GIT1 p.Ala515= (c.1545C>T) pathogenic?

GIT1 p.Ala515= (c.1545C>T) is classified Likely benign in GIT1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-12). Rare (popmax 0.203%, amr); Associated with GIT1-related disorder.

What condition is associated with GIT1 p.Ala515= (c.1545C>T)?

GIT1 p.Ala515= (c.1545C>T) is associated with GIT1-related disorder (ClinVar).

How common is GIT1 p.Ala515= (c.1545C>T) in the general population?

GIT1 p.Ala515= (c.1545C>T) is rare (popmax 0.203%, amr) (gnomAD).

GIT1 p.Ala515=

c.1545C>T · rs148402352 · VCV3034196

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.203%, amr)

Conditions

GIT1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 0.78, phastCons 1
Overall
CADD	7.942	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.203% Admixed American · 122/60,016 alleles

Filtering AF 0.174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.163%

Overall 0.034% 548/1,612,566 alleles · rare exomes 461/1,460,236 · genomes 87/152,330 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.203%	492
European (non-Finnish)	0.034%	2,942
Remaining individualsnot grpmax-eligible	0.0272%	3,674
African / African-American	0.00933%	10,722
East Asian	0.00223%	44,838

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.Ala515=
Coding: c.1545C>T
MANE Select: NM_014030
dbSNP: rs148402352
Type: single nucleotide variant
Location: chr17:29576286 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.72
Residue 515: 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

GIT1-related disorder

Similar variants

GIT1 p.Ala515fs Pathogenic ★ same residue
GIT1 p.Ala515Ser Uncertain significance ★ ⚠ same residue
GIT1 c.2010-4G>A Likely benign same condition
GIT1 p.Arg717= Likely benign same condition
GIT1 p.Asp418= Likely benign same condition
GIT1 p.Gln250= Likely benign same condition
GIT1 p.Glu221= Likely benign same condition
GIT1 p.Glu622= Likely benign 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-ala515 (accessed [today's date]).

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