Is CADM3 p.Ala376= (c.1128G>A) pathogenic?

CADM3 p.Ala376= (c.1128G>A) is classified Likely benign in CADM3 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-01). Very rare (popmax 0.00897%, eas).

How common is CADM3 p.Ala376= (c.1128G>A) in the general population?

CADM3 p.Ala376= (c.1128G>A) is very rare (popmax 0.00897%, eas) (gnomAD).

CADM3 p.Ala376=

c.1128G>A · VCV4821880

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00897%, eas)

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 -3.9	GERP -4.6
Overall
CADD	3.786	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00897% East Asian · 4/44,594 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00181%

Overall 0.00123% 18/1,459,034 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00897%	11,148
African / African-American	0.00267%	37,436
Finnishnot grpmax-eligible	0.00156%	63,972
European (non-Finnish)	0.000933%	107,141

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: CADM3
Protein: p.Ala376=
Coding: c.1128G>A
MANE Select: NM_001127173
Type: single nucleotide variant
Location: chr1:159200853 (GRCh38)
Gene constraint: LOEUF 0.381 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.97 · 1 PDB
Residue 376: the 'disordered' region

Full CADM3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CADM3 p.Ala376Val Uncertain significance ★ ⚠ same residue
CADM3 p.Tyr138Cys Likely pathogenic ★★ ⚠ same type
CADM3 c.89-2102C>T Uncertain significance ★★ same type
CADM3 p.Leu13Gln Uncertain significance ★★ ⚠ same type
CADM3 p.Tyr354Cys Uncertain significance ★★ ⚠ same type
CADM3 c.229+11A>G Uncertain significance ★ same type
CADM3 c.382+1G>A Uncertain significance ★ same type
CADM3 c.89-2118G>A 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/cadm3-p-ala376 (accessed [today's date]).

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