Is CA7 p.Leu51Phe (c.151C>T) pathogenic?

CA7 p.Leu51Phe (c.151C>T) is classified Uncertain significance in CA7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-31). AlphaMissense: likely benign (0.1236); Absent from gnomAD v4.1.

How common is CA7 p.Leu51Phe (c.151C>T) in the general population?

CA7 p.Leu51Phe (c.151C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CA7 p.Leu51Phe (c.151C>T)?

AlphaMissense predicts likely benign (score 0.1236) — an in-silico prediction, not a clinical call.

CA7 p.Leu51Phe

c.151C>T · VCV3826466

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1236 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1236	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -3.22	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 0.89	GERP -3.7, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 9,007 bp · p 3.9e-13 · regional, not allelic
Overall
CADD	19.32	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: CA7
Protein: p.Leu51Phe
Coding: c.151C>T
MANE Select: NM_005182
Type: single nucleotide variant
Location: chr16:66847140 (GRCh38)
Gene constraint: LOEUF 0.566 · pLI 0.88 (gnomAD)
Structure: AlphaFold pLDDT 97.15 · 13 PDB
Residue 51: the alpha-carbonic anhydrase domain; a β-strand

Full CA7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CA7 p.Ala165Val Uncertain significance ★ ⚠ same type
CA7 p.Ala55Asp Uncertain significance ★ ⚠ same type
CA7 p.Ala55Gly Uncertain significance ★ ⚠ same type
CA7 p.Arg161Leu Uncertain significance ★ ⚠ same type
CA7 p.Arg191Trp Uncertain significance ★ ⚠ same type
CA7 p.Arg215Trp Uncertain significance ★ ⚠ same type
CA7 p.Arg256His Uncertain significance ★ ⚠ same type
CA7 p.Arg263Gln 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/ca7-p-leu51phe (accessed [today's date]).

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