Is GRK2 p.Ala367Val (c.1100C>T) pathogenic?

GRK2 p.Ala367Val (c.1100C>T) is classified Likely benign in GRK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-01). AlphaMissense: ambiguous (0.5127); Very rare (popmax 0.0039%, nfe).

How common is GRK2 p.Ala367Val (c.1100C>T) in the general population?

GRK2 p.Ala367Val (c.1100C>T) is very rare (popmax 0.0039%, nfe) (gnomAD).

What do computational predictors say about GRK2 p.Ala367Val (c.1100C>T)?

AlphaMissense predicts ambiguous (score 0.5127) — an in-silico prediction, not a clinical call.

GRK2 p.Ala367Val

c.1100C>T · rs138698093 · VCV2642011

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5127 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0039%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5127	ambiguous
REVEL	0.206	benign-leaning
SaProt	LLR -12.40	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 3,262 bp · p 3.7e-19 · regional, not allelic
Overall
CADD	25.4	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 0.0039% European (non-Finnish) · 46/1,179,968 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00267%

Overall 0.0178% 287/1,613,502 alleles · very rare exomes 256/1,461,360 · genomes 31/152,142 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.693%	144
Remaining individualsnot grpmax-eligible	0.0576%	1,735
European (non-Finnish)grpmax	0.0039%	25,651

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: GRK2
Protein: p.Ala367Val
Coding: c.1100C>T
MANE Select: NM_001619
dbSNP: rs138698093
Type: single nucleotide variant
Location: chr11:67282482 (GRCh38)
Gene constraint: LOEUF 0.29 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.36 · 20 PDB
Residue 367: the protein kinase domain

Full GRK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GRK2 p.Ter690= Benign ★★ same type
GRK2 p.Tyr553= Benign ★★ same type
GRK2 c.503+1G>A Uncertain significance ★ same type
GRK2 p.Arg435Gln Uncertain significance ★ ⚠ same type
GRK2 p.Asp481Asn Uncertain significance ★ ⚠ same type
GRK2 p.Asp527Asn Uncertain significance ★ ⚠ same type
GRK2 p.Ser121Leu Uncertain significance ★ ⚠ same type
GRK2 p.Thr528Ile 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/grk2-p-ala367val (accessed [today's date]).

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