Is GRK5 p.Ala119Val (c.356C>T) pathogenic?

GRK5 p.Ala119Val (c.356C>T) is classified Benign in GRK5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-29). AlphaMissense: likely benign (0.0824); Low-frequency (popmax 1.32%, nfe).

How common is GRK5 p.Ala119Val (c.356C>T) in the general population?

GRK5 p.Ala119Val (c.356C>T) is low-frequency (popmax 1.32%, nfe) (gnomAD).

What do computational predictors say about GRK5 p.Ala119Val (c.356C>T)?

AlphaMissense predicts likely benign (score 0.0824) — an in-silico prediction, not a clinical call.

GRK5 p.Ala119Val

c.356C>T · rs55980792 · VCV773238

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0824 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.32%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0824	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -7.76	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.2, phastCons 0.31
Regional constraint	o/e 0.79	unconstrained · MANE · 247 kb · p 4.3e-09 · regional, not allelic
Overall
CADD	21.0	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 1.32% European (non-Finnish) · 15,567/1,179,036 alleles

Filtering AF 1.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.3%

Overall 1.04% 16,831/1,613,126 alleles · low-frequency

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.32%	76
Remaining individualsnot grpmax-eligible	0.888%	113
Finnishnot grpmax-eligible	0.391%	256
Admixed American	0.363%	275
African / African-American	0.229%	436
Ashkenazi Jewishnot grpmax-eligible	0.162%	617
Middle Eastern	0.033%	3,031
South Asian	0.0209%	4,793

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: GRK5
Protein: p.Ala119Val
Coding: c.356C>T
MANE Select: NM_005308
dbSNP: rs55980792
Type: single nucleotide variant
Location: chr10:119423182 (GRCh38)
Gene constraint: LOEUF 0.604 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 90.75 · 23 PDB
Residue 119: the rgs domain; a UniProt-annotated variant site (in); the 'n-terminal' region

Full GRK5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GRK5 c.440+10G>A Likely benign ★★ same type
GRK5 c.440+9C>T Benign ★★ same type
GRK5 p.Leu141Ile Benign ★★ same type
GRK5 p.Phe448Leu Benign ★★ same type
GRK5 p.Ala471Thr Uncertain significance ★ ⚠ same type
GRK5 p.Arg169His Uncertain significance ★ ⚠ same type
GRK5 p.Arg206Trp Uncertain significance ★ ⚠ same type
GRK5 p.Arg216Cys 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/grk5-p-ala119val (accessed [today's date]).

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