Is CALHM6 p.Pro110= (c.330C>T) pathogenic?

CALHM6 p.Pro110= (c.330C>T) is classified Likely benign in CALHM6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). Ultra-rare (popmax 0.0462%, nfe).

How common is CALHM6 p.Pro110= (c.330C>T) in the general population?

CALHM6 p.Pro110= (c.330C>T) is ultra-rare (popmax 0.0462%, nfe) (gnomAD).

CALHM6 p.Pro110=

c.330C>T · rs11544159 · VCV2656864

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0462%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.9	GERP -3.7
Overall
CADD	11.34	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0462% European (non-Finnish) · 496/1,073,374 alleles

Filtering AF 0.0428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0415%

Overall 0.0382% 526/1,378,674 alleles · ultra-rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.219%	456
European (non-Finnish)grpmax	0.0462%	2,164
Admixed American	0.0359%	2,783
Remaining individualsnot grpmax-eligible	0.0209%	4,794
Finnishnot grpmax-eligible	0.00494%	20,250
Ashkenazi Jewishnot grpmax-eligible	0.00477%	20,960
South Asian	0.00333%	30,023
African / African-American	0.00303%	32,951

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CALHM6
Protein: p.Pro110=
Coding: c.330C>T
MANE Select: NM_001010919
dbSNP: rs11544159
Type: single nucleotide variant
Location: chr6:116462259 (GRCh38)
Gene constraint: LOEUF 1.966 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.83 · 2 PDB
Residue 110: 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.Ala62Ser 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

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-pro110 (accessed [today's date]).

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