Is CLCA2 p.Ala680Val (c.2039C>T) pathogenic?

CLCA2 p.Ala680Val (c.2039C>T) is classified Uncertain significance in CLCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-24). AlphaMissense: likely benign (0.081); Absent from gnomAD v4.1.

How common is CLCA2 p.Ala680Val (c.2039C>T) in the general population?

CLCA2 p.Ala680Val (c.2039C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLCA2 p.Ala680Val (c.2039C>T)?

AlphaMissense predicts likely benign (score 0.081) — an in-silico prediction, not a clinical call.

CLCA2 p.Ala680Val

c.2039C>T · rs2524446048 · VCV2297314

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.081 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,840)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.081	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -6.28	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.23	donor gain · deltas
Constraint at this position
Conservation	phyloP 3.3	GERP -2.7, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 31 kb · p 0.29 · regional, not allelic
Overall
CADD	22.9	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 1,612,840). 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: CLCA2
Protein: p.Ala680Val
Coding: c.2039C>T
MANE Select: NM_006536
dbSNP: rs2524446048
Type: single nucleotide variant
Location: chr1:86450617 (GRCh38)
Gene constraint: LOEUF 1.144 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.87

Full CLCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLCA2 p.Leu169Phe Uncertain significance ★★ ⚠ same type
CLCA2 p.Gln842= Benign ★★ same type
CLCA2 p.Thr845= Benign ★★ same type
CLCA2 p.Tyr155= Benign ★★ same type
CLCA2 c.475+2T>A Uncertain significance ★ same type
CLCA2 p.Ala109Val Uncertain significance ★ ⚠ same type
CLCA2 p.Ala238Val Uncertain significance ★ ⚠ same type
CLCA2 p.Ala262Thr 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/clca2-p-ala680val (accessed [today's date]).

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