Is GIT1 p.Asp418= (c.1254C>T) pathogenic?

GIT1 p.Asp418= (c.1254C>T) is classified Likely benign in GIT1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-07). Ultra-rare (popmax 0.0418%, nfe); Associated with GIT1-related disorder.

What condition is associated with GIT1 p.Asp418= (c.1254C>T)?

GIT1 p.Asp418= (c.1254C>T) is associated with GIT1-related disorder (ClinVar).

How common is GIT1 p.Asp418= (c.1254C>T) in the general population?

GIT1 p.Asp418= (c.1254C>T) is ultra-rare (popmax 0.0418%, nfe) (gnomAD).

GIT1 p.Asp418=

c.1254C>T · rs199698909 · VCV3048055

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0418%, nfe)

Conditions

GIT1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP -7.9	GERP -3.8
Overall
CADD	1.116	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0418% European (non-Finnish) · 493/1,179,994 alleles

Filtering AF 0.0387% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0375%

Overall 0.0347% 560/1,613,866 alleles · ultra-rare exomes 520/1,461,652 · genomes 40/152,214 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0864%	1,157
European (non-Finnish)grpmax	0.0418%	2,393
African / African-American	0.00667%	14,986
Finnishnot grpmax-eligible	0.0047%	21,289
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
East Asian	0.00223%	44,898
South Asian	0.0022%	45,544
Admixed American	0.00167%	60,006

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp418=
Coding: c.1254C>T
MANE Select: NM_014030
dbSNP: rs199698909
Type: single nucleotide variant
Location: chr17:29576648 (GRCh38)
Gene constraint: LOEUF 0.257 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.72
Residue 418: the 'interaction with nck2 and grin3a' region; the 'required for localization at synapses' region; the 'interaction with mapk1' region

Full GIT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

GIT1-related disorder

Similar variants

GIT1 c.2010-4G>A Likely benign same condition
GIT1 p.Ala515= Likely benign same condition
GIT1 p.Arg717= 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
GIT1 p.His50= Likely benign same condition
GIT1 p.Leu516= 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-asp418 (accessed [today's date]).

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