Is GRB7 p.Pro388= (c.1164C>G) pathogenic?

GRB7 p.Pro388= (c.1164C>G) is classified Likely benign in GRB7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-01). Very rare (popmax 0.000678%, nfe).

How common is GRB7 p.Pro388= (c.1164C>G) in the general population?

GRB7 p.Pro388= (c.1164C>G) is very rare (popmax 0.000678%, nfe) (gnomAD).

GRB7 p.Pro388=

c.1164C>G · rs61754642 · VCV2647724

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

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 -1.6	GERP -5.1
Overall
CADD	5.311	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,180,014 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,613,888 alleles · very rare exomes 7/1,461,692 · genomes 1/152,196 · 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: GRB7
Protein: p.Pro388=
Coding: c.1164C>G
MANE Select: NM_005310
dbSNP: rs61754642
Type: single nucleotide variant
Location: chr17:39745493 (GRCh38)
Gene constraint: LOEUF 0.923 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.04 · 14 PDB

Full GRB7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GRB7 c.1210-4A>G Benign ★★ same type
GRB7 c.307-4G>A Benign ★★ same type
GRB7 p.Pro362Leu Benign ★★ same type
GRB7 p.Thr419Lys Benign ★★ same type
GRB7 c.-17T>C Uncertain significance ★ same type
GRB7 c.-2C>A Uncertain significance ★ same type
GRB7 c.-45G>A Uncertain significance ★ same type
GRB7 c.-50G>A Uncertain significance ★ same type

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/grb7-p-pro388 (accessed [today's date]).

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