Is CA8 p.Ile242Val (c.724A>G) pathogenic?

CA8 p.Ile242Val (c.724A>G) is classified Uncertain significance in CA8 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-10-14). AlphaMissense: likely benign (0.0858); Ultra-rare (popmax 0.0383%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CA8 p.Ile242Val (c.724A>G)?

CA8 p.Ile242Val (c.724A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CA8 p.Ile242Val (c.724A>G) in the general population?

CA8 p.Ile242Val (c.724A>G) is ultra-rare (popmax 0.0383%, nfe) (gnomAD).

What do computational predictors say about CA8 p.Ile242Val (c.724A>G)?

AlphaMissense predicts likely benign (score 0.0858) — an in-silico prediction, not a clinical call.

CA8 p.Ile242Val

c.724A>G · rs138405228 · VCV1757896

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0858 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0383%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0858	likely benign
REVEL	0.094	moderately benign-leaning
SaProt	LLR -6.11	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 6.2	GERP 1.4, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 57 kb · p 0.00026 · regional, not allelic
Overall
CADD	19.4	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

Grpmax group 0.0383% European (non-Finnish) · 447/1,166,678 alleles

Filtering AF 0.0353% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0341%

Overall 0.0316% 506/1,599,648 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0383%	2,610
Finnishnot grpmax-eligible	0.0281%	3,558
Remaining individualsnot grpmax-eligible	0.0226%	4,430
Admixed American	0.0217%	4,616
Middle Eastern	0.0166%	6,040
African / African-American	0.016%	6,232
South Asian	0.0011%	90,828

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: CA8
Protein: p.Ile242Val
Coding: c.724A>G
MANE Select: NM_004056
dbSNP: rs138405228
Type: single nucleotide variant
Location: chr8:60222663 (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 242: the alpha-carbonic anhydrase domain; a β-strand

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.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
CA8 p.Pro103= Benign/Likely 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-ile242val (accessed [today's date]).

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