Is GRIP1 p.Val80= (c.240A>G) pathogenic?

GRIP1 p.Val80= (c.240A>G) is classified Conflicting classifications of pathogenicity in GRIP1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-09-04). Very rare (popmax 0.0011%, nfe); Associated with Fraser syndrome 3.

What condition is associated with GRIP1 p.Val80= (c.240A>G)?

GRIP1 p.Val80= (c.240A>G) is associated with Fraser syndrome 3 (ClinVar).

How common is GRIP1 p.Val80= (c.240A>G) in the general population?

GRIP1 p.Val80= (c.240A>G) is very rare (popmax 0.0011%, nfe) (gnomAD).

GRIP1 p.Val80=

c.240A>G · rs886049799 · VCV310315

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Conditions

Fraser syndrome 3

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 -7.8	GERP -3.8
Overall
CADD	0.363	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% European (non-Finnish) · 13/1,179,932 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000805% 13/1,614,104 alleles · very rare exomes 13/1,461,772 · genomes 0/152,332 · 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.Val80=
Coding: c.240A>G
MANE Select: NM_001366722
dbSNP: rs886049799
Type: single nucleotide variant
Location: chr12:66541847 (GRCh38)
Structure: AlphaFold pLDDT 89.07
Residue 80: the galectin 1 domain

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.Val80Ala 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
GRIP1 p.Ala36Val 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-val80 (accessed [today's date]).

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