Is CA6 p.Val201Ile (c.601G>A) pathogenic?

CA6 p.Val201Ile (c.601G>A) is classified Likely benign in CA6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-12). AlphaMissense: likely benign (0.0836); Very rare (popmax 0.00585%, nfe).

How common is CA6 p.Val201Ile (c.601G>A) in the general population?

CA6 p.Val201Ile (c.601G>A) is very rare (popmax 0.00585%, nfe) (gnomAD).

What do computational predictors say about CA6 p.Val201Ile (c.601G>A)?

AlphaMissense predicts likely benign (score 0.0836) — an in-silico prediction, not a clinical call.

CA6 p.Val201Ile

c.601G>A · rs140314132 · VCV3136146

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0836 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00585%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0836	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -5.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.46 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.5	GERP -2.8
Regional constraint	o/e 0.99	unconstrained · MANE · 29 kb · p 0.8 · regional, not allelic
Overall
CADD	0.009	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 0.00585% European (non-Finnish) · 69/1,179,994 alleles

Filtering AF 0.0047% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00431%

Overall 0.00489% 79/1,613,926 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00585%	17,101
Remaining individualsnot grpmax-eligible	0.0048%	20,828
East Asian	0.00445%	22,447
African / African-American	0.00401%	24,961
South Asian	0.0022%	45,543

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: CA6
Protein: p.Val201Ile
Coding: c.601G>A
MANE Select: NM_001215
dbSNP: rs140314132
Type: single nucleotide variant
Location: chr1:8967688 (GRCh38)
Gene constraint: LOEUF 1.218 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.49 · 1 PDB
Residue 201: a disulfide bond; the alpha-carbonic anhydrase domain; an α-helix

Full CA6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CA6 p.Gly70= Benign ★★ same type
CA6 p.Ala33Val Uncertain significance ★ ⚠ same type
CA6 p.Arg255Cys Uncertain significance ★ ⚠ same type
CA6 p.Arg255Ser Uncertain significance ★ ⚠ same type
CA6 p.Arg265Gly Uncertain significance ★ ⚠ same type
CA6 p.Arg305Gly Uncertain significance ★ ⚠ same type
CA6 p.Arg96Gly Uncertain significance ★ ⚠ same type
CA6 p.Asn280Tyr 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/ca6-p-val201ile (accessed [today's date]).

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