Is GRIP1 p.Ser970Arg (c.2910C>A) pathogenic?

GRIP1 p.Ser970Arg (c.2910C>A) is classified Uncertain significance in GRIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-29). AlphaMissense: likely pathogenic (0.9845); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with GRIP1 p.Ser970Arg (c.2910C>A)?

GRIP1 p.Ser970Arg (c.2910C>A) is associated with Inborn genetic diseases (ClinVar).

How common is GRIP1 p.Ser970Arg (c.2910C>A) in the general population?

GRIP1 p.Ser970Arg (c.2910C>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about GRIP1 p.Ser970Arg (c.2910C>A)?

AlphaMissense predicts likely pathogenic (score 0.9845) — an in-silico prediction, not a clinical call.

GRIP1 p.Ser970Arg

c.2910C>A · VCV4032485

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9845 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9845	likely pathogenic · top 1% in GRIP1
REVEL	0.445	indeterminate
SaProt	LLR -9.33	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 1.1, phastCons 1
Overall
CADD	23.0	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 0.0011% South Asian · 1/91,092 alleles

Overall 6.2e-05% 1/1,614,060 alleles · very rare exomes 1/1,461,744 · genomes 0/152,316 · 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: GRIP1
Protein: p.Ser970Arg
Coding: c.2910C>A
MANE Select: NM_001366722
Type: single nucleotide variant
Location: chr12:66371796 (GRCh38)
Structure: AlphaFold pLDDT 89.07

Full GRIP1 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

GRIP1 p.Ser970Asn Uncertain significance ★ ⚠ same residue
GRIP1 p.Ala170Thr Uncertain significance ★★ ⚠ same condition
GRIP1 p.Ala894Val Uncertain significance ★★ ⚠ same condition
GRIP1 p.Arg869Trp Uncertain significance ★★ ⚠ same condition
GRIP1 p.Arg957His Uncertain significance ★★ ⚠ same condition
GRIP1 p.Asn528Ser Uncertain significance ★★ ⚠ same condition
GRIP1 p.Asp627Gly Uncertain significance ★★ ⚠ same condition
GRIP1 p.Glu993Lys 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-ser970arg (accessed [today's date]).

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