Is GRK5 p.Asp52Val (c.155A>T) pathogenic?

GRK5 p.Asp52Val (c.155A>T) is classified Uncertain significance in GRK5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). AlphaMissense: likely benign (0.2651); Very rare (popmax 0.0033%, sas).

How common is GRK5 p.Asp52Val (c.155A>T) in the general population?

GRK5 p.Asp52Val (c.155A>T) is very rare (popmax 0.0033%, sas) (gnomAD).

What do computational predictors say about GRK5 p.Asp52Val (c.155A>T)?

AlphaMissense predicts likely benign (score 0.2651) — an in-silico prediction, not a clinical call.

GRK5 p.Asp52Val

c.155A>T · rs561959438 · VCV2607920

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2651 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0033%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2651	likely benign
REVEL	0.435	indeterminate
SaProt	LLR -12.62	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 247 kb · p 4.3e-09 · regional, not allelic
Overall
CADD	25.7	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 0.0033% South Asian · 3/90,858 alleles

Filtering AF 0.000877% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000436% 7/1,605,812 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0033%	30,286
Remaining individualsnot grpmax-eligible	0.00322%	31,099
East Asian	0.00223%	44,772
European (non-Finnish)	8.53e-05%	1,172,692

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.Asp52Val
Coding: c.155A>T
MANE Select: NM_005308
dbSNP: rs561959438
Type: single nucleotide variant
Location: chr10:119380821 (GRCh38)
Gene constraint: LOEUF 0.604 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 90.75 · 23 PDB
Residue 52: the 'n-terminal' region

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

Similar variants

GRK5 p.Asp52Glu Uncertain significance ★ ⚠ same residue
GRK5 c.440+10G>A Likely benign ★★ same type
GRK5 c.440+9C>T Benign ★★ same type
GRK5 p.Ala119Val 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

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-asp52val (accessed [today's date]).

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