Is CALHM2 p.Val237Glu (c.710T>A) pathogenic?

CALHM2 p.Val237Glu (c.710T>A) is classified Uncertain significance in CALHM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-26). AlphaMissense: ambiguous (0.3844); Absent from gnomAD v4.1.

How common is CALHM2 p.Val237Glu (c.710T>A) in the general population?

CALHM2 p.Val237Glu (c.710T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CALHM2 p.Val237Glu (c.710T>A)?

AlphaMissense predicts ambiguous (score 0.3844) — an in-silico prediction, not a clinical call.

CALHM2 p.Val237Glu

c.710T>A · rs2540709887 · VCV3136699

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3844 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3844	ambiguous
REVEL	0.16	moderately benign-leaning
SaProt	LLR -6.51	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP 1.3, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 2,786 bp · p 0.24 · regional, not allelic
Overall
CADD	22.2	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: CALHM2
Protein: p.Val237Glu
Coding: c.710T>A
MANE Select: NM_015916
dbSNP: rs2540709887
Type: single nucleotide variant
Location: chr10:103447414 (GRCh38)
Gene constraint: LOEUF 1.212 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.52 · 12 PDB
Residue 237: the 'intersubunit interaction' region; an α-helix

Full CALHM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CALHM2 p.Ala110Val Uncertain significance ★ ⚠ same type
CALHM2 p.Ala243Thr Uncertain significance ★ ⚠ same type
CALHM2 p.Ala311Val Uncertain significance ★ ⚠ same type
CALHM2 p.Ala59Val Uncertain significance ★ ⚠ same type
CALHM2 p.Ala97Thr Uncertain significance ★ ⚠ same type
CALHM2 p.Arg109Cys Uncertain significance ★ ⚠ same type
CALHM2 p.Arg109His Uncertain significance ★ ⚠ same type
CALHM2 p.Arg10His 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/calhm2-p-val237glu (accessed [today's date]).

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