Is CA8 p.Pro160Leu (c.479C>T) pathogenic?

CA8 p.Pro160Leu (c.479C>T) is classified Uncertain significance in CA8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). AlphaMissense: likely benign (0.1815); Rare (popmax 0.119%, sas).

How common is CA8 p.Pro160Leu (c.479C>T) in the general population?

CA8 p.Pro160Leu (c.479C>T) is rare (popmax 0.119%, sas) (gnomAD).

What do computational predictors say about CA8 p.Pro160Leu (c.479C>T)?

AlphaMissense predicts likely benign (score 0.1815) — an in-silico prediction, not a clinical call.

CA8 p.Pro160Leu

c.479C>T · rs556165338 · VCV1879714

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1815 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.119%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1815	likely benign
REVEL	0.25	benign-leaning
SaProt	LLR -10.11	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 57 kb · p 0.00026 · regional, not allelic
Overall
CADD	25.5	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 0.119% South Asian · 108/91,084 alleles

Filtering AF 0.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0936%

Overall 0.0083% 134/1,613,984 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.119%	843
Middle Eastern	0.0165%	6,058
Admixed American	0.01%	10,001
African / African-American	0.008%	12,503
Remaining individualsnot grpmax-eligible	0.0048%	20,831
European (non-Finnish)	0.000848%	117,990

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.Pro160Leu
Coding: c.479C>T
MANE Select: NM_004056
dbSNP: rs556165338
Type: single nucleotide variant
Location: chr8:60232318 (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 160: the alpha-carbonic anhydrase domain

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

Similar variants

CA8 p.Arg213Trp Uncertain significance ★★ ⚠ same type
CA8 p.Pro14Arg Uncertain significance ★★ ⚠ same type
CA8 p.Ser71Phe Uncertain significance ★★ ⚠ same type
CA8 c.100+154T>C Benign ★★ same type
CA8 c.100+19G>A Benign ★★ same type
CA8 c.100+37G>A Benign ★★ same type
CA8 c.100+81C>T Benign ★★ same type
CA8 c.100+85T>C Benign ★★ 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/ca8-p-pro160leu (accessed [today's date]).

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