Is CALCA p.Ala118Val (c.353C>T) pathogenic?

CALCA p.Ala118Val (c.353C>T) is classified Uncertain significance in CALCA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-09). Very rare (popmax 0.00223%, eas).

How common is CALCA p.Ala118Val (c.353C>T) in the general population?

CALCA p.Ala118Val (c.353C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

CALCA p.Ala118Val

c.353C>T · VCV3484336

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.031	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.1	GERP -3.3
Overall
CADD	6.289	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,876 alleles

Overall 0.000657% 1/152,306 alleles · very rare

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: CALCA
Protein: p.Ala118Val
Coding: c.353C>T
MANE Select: NM_001741 · reported on NM_001033953
Type: single nucleotide variant
Location: chr11:14967729 (GRCh38)
Gene constraint: LOEUF 1.186 · pLI 0.13 (gnomAD)
Structure: AlphaFold pLDDT 64.12 · 6 PDB
Residue 118: the 'disordered' region

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

Similar variants

CALCA p.Phe106= Benign ★★ same type
CALCA p.Ala11Thr Uncertain significance ★ ⚠ same type
CALCA p.Ala31Ser Uncertain significance ★ ⚠ same type
CALCA p.Ala47Pro Uncertain significance ★ ⚠ same type
CALCA p.Ala47Val Uncertain significance ★ ⚠ same type
CALCA p.Arg123Cys Uncertain significance ★ same type
CALCA p.Arg84Gln Uncertain significance ★ ⚠ same type
CALCA p.Arg84Pro 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/calca-p-ala118val (accessed [today's date]).

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