Is CALU p.Val90Met (c.268G>A) pathogenic?

CALU p.Val90Met (c.268G>A) is classified Uncertain significance in CALU (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-20). AlphaMissense: likely benign (0.1267); Absent from gnomAD v4.1.

How common is CALU p.Val90Met (c.268G>A) in the general population?

CALU p.Val90Met (c.268G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CALU p.Val90Met (c.268G>A)?

AlphaMissense predicts likely benign (score 0.1267) — an in-silico prediction, not a clinical call.

CALU p.Val90Met

c.268G>A · rs2536247829 · VCV2268315

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1267 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1267	likely benign
REVEL	0.19	benign-leaning
SaProt	LLR -9.11	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 12	phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 21 kb · p 3e-08 · regional, not allelic
Overall
CADD	23.8	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

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: CALU
Protein: p.Val90Met
Coding: c.268G>A
MANE Select: NM_001219
dbSNP: rs2536247829
Type: single nucleotide variant
Location: chr7:128754308 (GRCh38)
Gene constraint: LOEUF 0.556 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 79.82
Residue 90: the ef-hand 1 domain

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

Similar variants

OPN1SW p.Ala309Pro Uncertain significance ★★ ⚠ same type
OPN1SW p.Ser335Phe Uncertain significance ★★ ⚠ same type
OPN1SW p.Ser324= Likely benign ★★ same type
OPN1SW p.Ser338= Benign/Likely benign ★★ same type
CALU p.Arg234Ter Likely pathogenic ★ same type
CALU c.-11-208C>G Uncertain significance ★ same type
CALU c.-3A>G Uncertain significance ★ same type
CALU c.*3456C>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/calu-p-val90met (accessed [today's date]).

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