Is CA5A p.Val145Ala (c.434T>C) pathogenic?

CA5A p.Val145Ala (c.434T>C) is classified Uncertain significance in CA5A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-12). AlphaMissense: likely benign (0.3235); Very rare (popmax 0.00223%, eas).

How common is CA5A p.Val145Ala (c.434T>C) in the general population?

CA5A p.Val145Ala (c.434T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CA5A p.Val145Ala (c.434T>C)?

AlphaMissense predicts likely benign (score 0.3235) — an in-silico prediction, not a clinical call.

CA5A p.Val145Ala

c.434T>C · VCV4282195

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3235 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3235	likely benign
REVEL	0.767	pathogenic-leaning
SaProt	LLR -12.85	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 48 kb · p 0.027 · regional, not allelic
Overall
CADD	23.0	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

Grpmax group 0.00223% East Asian · 1/44,866 alleles

Overall 6.85e-05% 1/1,458,856 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CA5A
Protein: p.Val145Ala
Coding: c.434T>C
MANE Select: NM_001739
Type: single nucleotide variant
Location: chr16:87904811 (GRCh38)
Gene constraint: LOEUF 1.257 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.38
Residue 145: the alpha-carbonic anhydrase domain

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

Similar variants

CA5A p.Val145Met Uncertain significance ★★ ⚠ same residue
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

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-val145ala (accessed [today's date]).

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