Is GRIP1 p.Ser960= (c.2880G>A) pathogenic?

GRIP1 p.Ser960= (c.2880G>A) is classified Benign/Likely benign in GRIP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-28). Rare (popmax 0.794%, afr); Associated with Fraser syndrome 3.

What condition is associated with GRIP1 p.Ser960= (c.2880G>A)?

GRIP1 p.Ser960= (c.2880G>A) is associated with Fraser syndrome 3 (ClinVar).

How common is GRIP1 p.Ser960= (c.2880G>A) in the general population?

GRIP1 p.Ser960= (c.2880G>A) is rare (popmax 0.794%, afr) (gnomAD).

GRIP1 p.Ser960=

c.2880G>A · rs181527317 · VCV710021

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.794%, afr)

Conditions

Fraser syndrome 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.087	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13	GERP -5.9
Overall
CADD	0.066	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.794% African / African-American · 596/75,038 alleles

Filtering AF 0.741% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.72%

Overall 0.0431% 695/1,613,828 alleles · rare exomes 354/1,461,526 · genomes 341/152,302 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.794%	126
Middle Eastern	0.0835%	1,197
Admixed American	0.0633%	1,580
Remaining individualsnot grpmax-eligible	0.0496%	2,016
European (non-Finnish)	0.00212%	47,192

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: GRIP1
Protein: p.Ser960=
Coding: c.2880G>A
MANE Select: NM_001366722
dbSNP: rs181527317
Type: single nucleotide variant
Location: chr12:66371826 (GRCh38)
Structure: AlphaFold pLDDT 89.07

Full GRIP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Fraser syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GRIP1 p.Ser960Leu Uncertain significance ★ ⚠ same residue
GRIP1 p.Ser960Trp Uncertain significance ★ ⚠ same residue
GRIP1 p.Cys10Ter Pathogenic/Likely pathogenic ★★ same condition
GRIP1 c.55+3A>C Uncertain significance ★★ same condition
GRIP1 c.-172A>G Uncertain significance ★★ same condition
GRIP1 c.*99G>A Uncertain significance ★★ same condition
GRIP1 p.Ala170Thr Uncertain significance ★★ ⚠ same condition
GRIP1 p.Ala261Thr 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/grip1-p-ser960 (accessed [today's date]).

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