Is CALHM6 p.Ala62Ser (c.184G>T) pathogenic?

CALHM6 p.Ala62Ser (c.184G>T) is classified Uncertain significance in CALHM6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). AlphaMissense: likely benign (0.2163); Absent from gnomAD v4.1.

How common is CALHM6 p.Ala62Ser (c.184G>T) in the general population?

CALHM6 p.Ala62Ser (c.184G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CALHM6 p.Ala62Ser (c.184G>T)?

AlphaMissense predicts likely benign (score 0.2163) — an in-silico prediction, not a clinical call.

CALHM6 p.Ala62Ser

c.184G>T · rs1784785436 · VCV2597798

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2163 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,541,748)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2163	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -7.62	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 2.1	GERP -0.17, phastCons 0.28
Regional constraint	o/e 1.03	unconstrained · MANE · 1,772 bp · p 0.53 · regional, not allelic
Overall
CADD	21.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,541,748). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CALHM6
Protein: p.Ala62Ser
Coding: c.184G>T
MANE Select: NM_001010919
dbSNP: rs1784785436
Type: single nucleotide variant
Location: chr6:116462113 (GRCh38)
Gene constraint: LOEUF 1.966 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.83 · 2 PDB
Residue 62: a disulfide bond

Full CALHM6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CALHM6 p.Ala233Val Uncertain significance ★ ⚠ same type
CALHM6 p.Ala36Asp Uncertain significance ★ ⚠ same type
CALHM6 p.Arg144Ser Uncertain significance ★ ⚠ same type
CALHM6 p.Arg73Gly Uncertain significance ★ ⚠ same type
CALHM6 p.Asn143Lys Uncertain significance ★ ⚠ same type
CALHM6 p.Asn236Ser Uncertain significance ★ ⚠ same type
CALHM6 p.Asn267Ser Uncertain significance ★ ⚠ same type
CALHM6 p.Cys155Tyr 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/calhm6-p-ala62ser (accessed [today's date]).

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