Is CLCA4 p.Gly319Ser (c.955G>A) pathogenic?

CLCA4 p.Gly319Ser (c.955G>A) is classified Likely benign in CLCA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). AlphaMissense: likely benign (0.0817); Very rare (popmax 0.00224%, eas).

How common is CLCA4 p.Gly319Ser (c.955G>A) in the general population?

CLCA4 p.Gly319Ser (c.955G>A) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about CLCA4 p.Gly319Ser (c.955G>A)?

AlphaMissense predicts likely benign (score 0.0817) — an in-silico prediction, not a clinical call.

CLCA4 p.Gly319Ser

c.955G>A · VCV3267542

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0817 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0817	likely benign
REVEL	0.326	indeterminate
SaProt	LLR -6.06	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.2
Regional constraint	o/e 1.03	unconstrained · MANE · 33 kb · p 0.26 · regional, not allelic
Overall
CADD	0.001	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00224% East Asian · 1/44,648 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000311% 5/1,605,936 alleles · very rare exomes 5/1,454,144 · genomes 0/151,792 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,648
Remaining individualsnot grpmax-eligible	0.00161%	62,204
European (non-Finnish)	0.000255%	391,771

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: CLCA4
Protein: p.Gly319Ser
Coding: c.955G>A
MANE Select: NM_012128
Type: single nucleotide variant
Location: chr1:86567424 (GRCh38)
Gene constraint: LOEUF 1.078 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.48
Residue 319: the vwfa domain

Full CLCA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLCA4 p.Asp510Gly Uncertain significance ★★ ⚠ same type
CLCA4 p.Gln485Ter Uncertain significance ★★ same type
CLCA4 p.Arg113= Benign/Likely benign ★★ same type
CLCA4 p.Ala235Thr Uncertain significance ★ ⚠ same type
CLCA4 p.Ala353Val Uncertain significance ★ same type
CLCA4 p.Ala431Thr Uncertain significance ★ ⚠ same type
CLCA4 p.Ala431Val Uncertain significance ★ ⚠ same type
CLCA4 p.Ala437Gly 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/clca4-p-gly319ser (accessed [today's date]).

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