Is CA5A p.Phe267Leu (c.799T>C) pathogenic?

CA5A p.Phe267Leu (c.799T>C) is classified Uncertain significance in CA5A (ClinVar, Single submitter, 1 submitter; last evaluated 2017-08-01). AlphaMissense: likely pathogenic (0.8222); Absent from gnomAD v4.1.

How common is CA5A p.Phe267Leu (c.799T>C) in the general population?

CA5A p.Phe267Leu (c.799T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CA5A p.Phe267Leu (c.799T>C)?

AlphaMissense predicts likely pathogenic (score 0.8222) — an in-silico prediction, not a clinical call.

CA5A p.Phe267Leu

c.799T>C · rs1555519114 · VCV493196

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8222 · 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	0.8222	likely pathogenic · top 9% in CA5A
REVEL	0.448	indeterminate
SaProt	LLR -9.27	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 0.68, phastCons 0.32
Regional constraint	o/e 1.11	unconstrained · MANE · 48 kb · p 0.027 · regional, not allelic
Overall
CADD	21.4	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: CA5A
Protein: p.Phe267Leu
Coding: c.799T>C
MANE Select: NM_001739
dbSNP: rs1555519114
Type: single nucleotide variant
Location: chr16:87888248 (GRCh38)
Gene constraint: LOEUF 1.257 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.38
Residue 267: the alpha-carbonic anhydrase domain

Full CA5A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CA5A p.Arg32Ter Pathogenic ★★ same type
CA5A p.Glu241Lys Pathogenic/Likely pathogenic ★★ same type
CA5A p.Ala149Thr Uncertain significance ★★ ⚠ same type
CA5A p.Ala208Val Uncertain significance ★★ ⚠ same type
CA5A p.Ala261Val Uncertain significance ★★ ⚠ same type
CA5A p.Arg26His Uncertain significance ★★ ⚠ same type
CA5A p.Asp216Ala Uncertain significance ★★ ⚠ same type
CA5A p.Gln79Glu 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/ca5a-p-phe267leu (accessed [today's date]).

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