Is GIT1 p.Ser570Ala (c.1708T>G) pathogenic?

GIT1 p.Ser570Ala (c.1708T>G) is classified Uncertain significance in GIT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-04). AlphaMissense: likely benign (0.0625); Very rare (popmax 0.00168%, amr); Associated with Inborn genetic diseases.

What condition is associated with GIT1 p.Ser570Ala (c.1708T>G)?

GIT1 p.Ser570Ala (c.1708T>G) is associated with Inborn genetic diseases (ClinVar).

How common is GIT1 p.Ser570Ala (c.1708T>G) in the general population?

GIT1 p.Ser570Ala (c.1708T>G) is very rare (popmax 0.00168%, amr) (gnomAD).

What do computational predictors say about GIT1 p.Ser570Ala (c.1708T>G)?

AlphaMissense predicts likely benign (score 0.0625) — an in-silico prediction, not a clinical call.

GIT1 p.Ser570Ala

c.1708T>G · rs758929748 · VCV3099909

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0625 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00168%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0625	likely benign
REVEL	0.166	moderately benign-leaning
SaProt	LLR -7.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.27	acceptor loss, 27 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 6.2	GERP -0.61, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 1,519 bp · p 0.045 · regional, not allelic
Overall
CADD	20.3	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 0.00168% Admixed American · 1/59,690 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,611,952 alleles · very rare exomes 4/1,459,712 · genomes 0/152,240 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00168%	59,690
European (non-Finnish)	0.000254%	393,035

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.Ser570Ala
Coding: c.1708T>G
MANE Select: NM_014030
dbSNP: rs758929748
Type: single nucleotide variant
Location: chr17:29575856 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.72
Residue 570: 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-ser570ala (accessed [today's date]).

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