Is CLCA1 p.Pro607Ser (c.1819C>T) pathogenic?

CLCA1 p.Pro607Ser (c.1819C>T) is classified Uncertain significance in CLCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-21). AlphaMissense: likely benign (0.1551); Absent from gnomAD v4.1.

How common is CLCA1 p.Pro607Ser (c.1819C>T) in the general population?

CLCA1 p.Pro607Ser (c.1819C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLCA1 p.Pro607Ser (c.1819C>T)?

AlphaMissense predicts likely benign (score 0.1551) — an in-silico prediction, not a clinical call.

CLCA1 p.Pro607Ser

c.1819C>T · rs2524537329 · VCV2338634

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1551 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1551	likely benign
REVEL	0.301	indeterminate
SaProt	LLR -8.69	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 5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 31 kb · p 0.017 · regional, not allelic
Overall
CADD	23.6	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: CLCA1
Protein: p.Pro607Ser
Coding: c.1819C>T
MANE Select: NM_001285
dbSNP: rs2524537329
Type: single nucleotide variant
Location: chr1:86494325 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.40 · 2 PDB

Full CLCA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLCA1 c.2113+8A>G Benign ★★ same type
CLCA1 p.Asn682Lys Benign ★★ same type
CLCA1 p.Tyr661His Benign ★★ ⚠ same type
CLCA1 p.Val609Ile Benign ★★ same type
CLCA1 p.Ala189Pro Uncertain significance ★ ⚠ same type
CLCA1 p.Ala436Thr Uncertain significance ★ ⚠ same type
CLCA1 p.Ala441Val Uncertain significance ★ ⚠ same type
CLCA1 p.Ala442Ser 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/clca1-p-pro607ser (accessed [today's date]).

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