Is CMKLR2 p.Ile307Val (c.919A>G) pathogenic?

CMKLR2 p.Ile307Val (c.919A>G) is classified Benign in CMKLR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-04-19). AlphaMissense: likely benign (0.1227); Common (popmax 64.2%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CMKLR2 p.Ile307Val (c.919A>G)?

AlphaMissense predicts likely benign (score 0.1227) — an in-silico prediction, not a clinical call.

CMKLR2 p.Ile307Val

Q: How common is CMKLR2 p.Ile307Val (c.919A>G) in the general population?

CMKLR2 p.Ile307Val (c.919A>G) is common (popmax 64.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.919A>G · rs3732083 · VCV1238518

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1227 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 64.2%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1227	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -4.80	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 4.1	GERP -0.17, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 1,064 bp · p 0.56 · regional, not allelic
Overall
CADD	17.44	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 64.2% African / African-American · 48,085/74,922 alleles

Filtering AF 63.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 63.5%

Overall 44.6% 719,785/1,613,662 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	64.2%	2
Ashkenazi Jewishnot grpmax-eligible	54.1%	2
Admixed American	52.5%	2
Middle Eastern	52.4%	2
Finnishnot grpmax-eligible	52.3%	2
Remaining individualsnot grpmax-eligible	45.6%	2
European (non-Finnish)	43.6%	2
South Asian	35.6%	3
Amishnot grpmax-eligible	32%	3
East Asian	26.7%	4

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: CMKLR2
Protein: p.Ile307Val
Coding: c.919A>G
MANE Select: NM_001389445
dbSNP: rs3732083
Type: single nucleotide variant
Location: chr2:206176329 (GRCh38)
Gene constraint: LOEUF 1.057 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.29 · 9 PDB
Residue 307: a UniProt-annotated variant site (in); a β-strand

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

Similar variants

CMKLR2 p.Ala165Val Uncertain significance ★ ⚠ 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-ile307val (accessed [today's date]).

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