Is CA8 p.Ala2Val (c.5C>T) pathogenic?

CA8 p.Ala2Val (c.5C>T) is classified Uncertain significance in CA8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-29). AlphaMissense: ambiguous (0.3479); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CA8 p.Ala2Val (c.5C>T)?

CA8 p.Ala2Val (c.5C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CA8 p.Ala2Val (c.5C>T) in the general population?

CA8 p.Ala2Val (c.5C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CA8 p.Ala2Val (c.5C>T)?

AlphaMissense predicts ambiguous (score 0.3479) — an in-silico prediction, not a clinical call.

CA8 p.Ala2Val

c.5C>T · rs761506746 · VCV3136154

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3479 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,564,218)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3479	ambiguous
REVEL	0.204	benign-leaning
SaProt	LLR -7.49	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 12	GERP 1.2, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 15 kb · p 0.24 · regional, not allelic
Overall
CADD	29.6	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

No allele count reported in gnomAD v4.1 (AN 1,564,218). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CA8
Protein: p.Ala2Val
Coding: c.5C>T
MANE Select: NM_004056
dbSNP: rs761506746
Type: single nucleotide variant
Location: chr8:60281143 (GRCh38)
Gene constraint: LOEUF 0.698 · pLI 0.24 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.51 · 1 PDB
Residue 2: the 'disordered' region

Full CA8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CA8 p.Ala2Glu Uncertain significance ★ ⚠ same residue
CA8 p.Pro14Arg Uncertain significance ★★ ⚠ same condition
CA8 p.Ser71Phe Uncertain significance ★★ ⚠ same condition
CA8 c.576+5G>A Benign/Likely benign ★★ same condition
CA8 p.Glu109= Benign ★★ same condition
CA8 p.Glu22= Benign ★★ same condition
CA8 p.Gly265= Benign/Likely benign ★★ same condition
CA8 p.Leu112= Benign ★★ same condition

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/ca8-p-ala2val (accessed [today's date]).

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