Is CMKLR2 p.Ala165Val (c.494C>T) pathogenic?

CMKLR2 p.Ala165Val (c.494C>T) is classified Uncertain significance in CMKLR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely pathogenic (0.751); Absent from gnomAD v4.1.

How common is CMKLR2 p.Ala165Val (c.494C>T) in the general population?

CMKLR2 p.Ala165Val (c.494C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CMKLR2 p.Ala165Val (c.494C>T)?

AlphaMissense predicts likely pathogenic (score 0.751) — an in-silico prediction, not a clinical call.

CMKLR2 p.Ala165Val

c.494C>T · VCV4654715

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.751 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.751	likely pathogenic
REVEL	0.659	pathogenic-leaning
SaProt	LLR -7.80	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 1,064 bp · p 0.56 · regional, not allelic
Overall
CADD	26.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CMKLR2
Protein: p.Ala165Val
Coding: c.494C>T
MANE Select: NM_001389445
Type: single nucleotide variant
Location: chr2:206176754 (GRCh38)
Gene constraint: LOEUF 1.057 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.29 · 9 PDB
Residue 165: a disulfide bond; an α-helix

Full CMKLR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CMKLR2 p.Ile307Val Benign ★★ same type
CMKLR2 p.Ala172Val Uncertain significance ★ ⚠ same type
CMKLR2 p.Ala80Asp Uncertain significance ★ ⚠ same type
CMKLR2 p.Ala82Val Uncertain significance ★ ⚠ same type
CMKLR2 p.Arg147Trp Uncertain significance ★ ⚠ same type
CMKLR2 p.Arg176Gln Uncertain significance ★ ⚠ same type
CMKLR2 p.Arg176Trp Uncertain significance ★ ⚠ same type
CMKLR2 p.Arg202Lys 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/cmklr2-p-ala165val (accessed [today's date]).

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