Is CA2 p.Leu147Phe (c.441G>T) pathogenic?

CA2 p.Leu147Phe (c.441G>T) is classified Uncertain significance in CA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-22). AlphaMissense: ambiguous (0.4407); Absent from gnomAD v4.1.

How common is CA2 p.Leu147Phe (c.441G>T) in the general population?

CA2 p.Leu147Phe (c.441G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CA2 p.Leu147Phe (c.441G>T)?

AlphaMissense predicts ambiguous (score 0.4407) — an in-silico prediction, not a clinical call.

CA2 p.Leu147Phe

c.441G>T · rs2536486889 · VCV2086498

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4407 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4407	ambiguous
REVEL	0.277	benign-leaning
SaProt	LLR -6.93	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 0.82, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 6,424 bp · p 0.35 · regional, not allelic
Overall
CADD	23.7	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: CA2
Protein: p.Leu147Phe
Coding: c.441G>T
MANE Select: NM_000067
dbSNP: rs2536486889
Type: single nucleotide variant
Location: chr8:85474413 (GRCh38)
Gene constraint: LOEUF 1.491 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.38 · 1249 PDB
Residue 147: the alpha-carbonic anhydrase domain; a β-strand

Full CA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CA2 c.232+1G>A Pathogenic ★★ same type
CA2 p.Gln92Pro Likely pathogenic ★★ same type
CA2 p.Glu204Ter Pathogenic/Likely pathogenic ★★ same type
CA2 p.Tyr193Ter Likely pathogenic ★★ same type
CA2 p.Arg181Cys Uncertain significance ★★ ⚠ same type
CA2 p.Arg181His Uncertain significance ★★ ⚠ same type
CA2 p.Arg226His Uncertain significance ★★ ⚠ same type
CA2 p.Arg245Cys 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/ca2-p-leu147phe (accessed [today's date]).

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