Is CLCA2 p.Ser320Arg (c.960C>G) pathogenic?

CLCA2 p.Ser320Arg (c.960C>G) is classified Uncertain significance in CLCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-06). AlphaMissense: likely benign (0.1341); Rare (popmax 0.124%, sas).

How common is CLCA2 p.Ser320Arg (c.960C>G) in the general population?

CLCA2 p.Ser320Arg (c.960C>G) is rare (popmax 0.124%, sas) (gnomAD).

What do computational predictors say about CLCA2 p.Ser320Arg (c.960C>G)?

AlphaMissense predicts likely benign (score 0.1341) — an in-silico prediction, not a clinical call.

CLCA2 p.Ser320Arg

c.960C>G · rs548989310 · VCV2461210

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1341 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.124%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1341	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -6.63	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 -0.54	GERP -1, phastCons 0.015
Regional constraint	o/e 0.97	unconstrained · MANE · 31 kb · p 0.29 · regional, not allelic
Overall
CADD	17.92	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

Grpmax group 0.124% South Asian · 113/90,922 alleles

Filtering AF 0.106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0986%

Overall 0.009% 145/1,610,734 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.124%	805
Remaining individualsnot grpmax-eligible	0.0385%	2,600
East Asian	0.0111%	8,970
Admixed American	0.00167%	59,972
European (non-Finnish)	0.00017%	588,523

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: CLCA2
Protein: p.Ser320Arg
Coding: c.960C>G
MANE Select: NM_006536
dbSNP: rs548989310
Type: single nucleotide variant
Location: chr1:86434733 (GRCh38)
Gene constraint: LOEUF 1.144 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.87
Residue 320: the vwfa domain

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-ser320arg (accessed [today's date]).

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