Is GRK7 p.Val398Phe (c.1192G>T) pathogenic?

GRK7 p.Val398Phe (c.1192G>T) is classified Uncertain significance in GRK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-17). AlphaMissense: likely benign (0.3127); Rare (popmax 0.245%, eas).

How common is GRK7 p.Val398Phe (c.1192G>T) in the general population?

GRK7 p.Val398Phe (c.1192G>T) is rare (popmax 0.245%, eas) (gnomAD).

What do computational predictors say about GRK7 p.Val398Phe (c.1192G>T)?

AlphaMissense predicts likely benign (score 0.3127) — an in-silico prediction, not a clinical call.

GRK7 p.Val398Phe

c.1192G>T · rs141435292 · VCV3102625

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3127 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.245%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3127	likely benign
REVEL	0.265	benign-leaning
SaProt	LLR -10.70	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.51	GERP -3.1, phastCons 0.001
Regional constraint	o/e 0.91	unconstrained · MANE · 39 kb · p 0.017 · regional, not allelic
Overall
CADD	18.5	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 0.245% East Asian · 110/44,886 alleles

Filtering AF 0.208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.194%

Overall 0.0264% 426/1,614,196 alleles · rare exomes 394/1,461,874 · genomes 32/152,322 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.245%	408
African / African-American	0.0373%	2,680
Admixed American	0.0283%	3,531
European (non-Finnish)	0.0208%	4,797
Remaining individualsnot grpmax-eligible	0.0176%	5,683
South Asian	0.00988%	10,121
Finnishnot grpmax-eligible	0.00781%	12,806

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: GRK7
Protein: p.Val398Phe
Coding: c.1192G>T
MANE Select: NM_139209
dbSNP: rs141435292
Type: single nucleotide variant
Location: chr3:141807786 (GRCh38)
Gene constraint: LOEUF 0.836 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.79
Residue 398: the protein kinase domain

Full GRK7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GRK7 p.Val398Ile Uncertain significance ★ ⚠ same residue
GRK7 p.Val398Leu Uncertain significance ★ ⚠ same residue
GRK7 p.Ala236Gly Uncertain significance ★ ⚠ same type
GRK7 p.Ala298Thr Uncertain significance ★ ⚠ same type
GRK7 p.Ala351Asp Uncertain significance ★ ⚠ same type
GRK7 p.Ala46Thr Uncertain significance ★ ⚠ same type
GRK7 p.Ala6Asp Uncertain significance ★ ⚠ same type
GRK7 p.Ala84Glu 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/grk7-p-val398phe (accessed [today's date]).

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