Is CA8 p.Leu112= (c.334C>T) pathogenic?

CA8 p.Leu112= (c.334C>T) is classified Benign in CA8 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-01-23). Common (popmax 16.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with CA8 p.Leu112= (c.334C>T)?

CA8 p.Leu112= (c.334C>T) is associated with Inborn genetic diseases (ClinVar).

CA8 p.Leu112=

Q: How common is CA8 p.Leu112= (c.334C>T) in the general population?

CA8 p.Leu112= (c.334C>T) is common (popmax 16.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.334C>T · rs61743130 · VCV128541

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 16.9%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 0.91, phastCons 1
Overall
CADD	9.997	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 16.9% African / African-American · 12,641/74,926 alleles

Filtering AF 16.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 16.5%

Overall 1.77% 28,513/1,613,452 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	16.9%	6
Middle Eastern	2.29%	44
Admixed American	2.08%	48
Remaining individualsnot grpmax-eligible	2.05%	49
European (non-Finnish)	1.07%	94
Amishnot grpmax-eligible	0.987%	101
Ashkenazi Jewishnot grpmax-eligible	0.608%	164
Finnishnot grpmax-eligible	0.425%	235
South Asian	0.172%	580

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.Leu112=
Coding: c.334C>T
MANE Select: NM_004056
dbSNP: rs61743130
Type: single nucleotide variant
Location: chr8:60266008 (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 112: 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.Pro103= Benign/Likely benign ★★ same condition
CA8 p.Ser100Leu 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-leu112 (accessed [today's date]).

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