Is CA14 p.Leu7Pro (c.20T>C) pathogenic?

CA14 p.Leu7Pro (c.20T>C) is classified Uncertain significance in CA14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-14). AlphaMissense: likely benign (0.1907); Absent from gnomAD v4.1.

How common is CA14 p.Leu7Pro (c.20T>C) in the general population?

CA14 p.Leu7Pro (c.20T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CA14 p.Leu7Pro (c.20T>C)?

AlphaMissense predicts likely benign (score 0.1907) — an in-silico prediction, not a clinical call.

CA14 p.Leu7Pro

c.20T>C · VCV3826445

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1907 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1907	likely benign
REVEL	0.562	indeterminate
SaProt	LLR -10.56	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,527 bp · p 0.45 · regional, not allelic
Overall
CADD	27.0	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

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: CA14
Protein: p.Leu7Pro
Coding: c.20T>C
MANE Select: NM_012113
Type: single nucleotide variant
Location: chr1:150258148 (GRCh38)
Gene constraint: LOEUF 1.167 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.11 · 2 PDB

Full CA14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CA14 p.Glu149= Benign ★★ same type
CA14 p.Ala158Gly Uncertain significance ★ ⚠ same type
CA14 p.Ala173Val Uncertain significance ★ ⚠ same type
CA14 p.Arg101Gln Uncertain significance ★ ⚠ same type
CA14 p.Arg211Gly Uncertain significance ★ ⚠ same type
CA14 p.Arg211His Uncertain significance ★ ⚠ same type
CA14 p.Arg232Gly Uncertain significance ★ ⚠ same type
CA14 p.Arg264Gln 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/ca14-p-leu7pro (accessed [today's date]).

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