Is CA9 p.Thr205Ile (c.614C>T) pathogenic?

CA9 p.Thr205Ile (c.614C>T) is classified Uncertain significance in CA9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-15). AlphaMissense: likely benign (0.1349); Absent from gnomAD v4.1.

How common is CA9 p.Thr205Ile (c.614C>T) in the general population?

CA9 p.Thr205Ile (c.614C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CA9 p.Thr205Ile (c.614C>T)?

AlphaMissense predicts likely benign (score 0.1349) — an in-silico prediction, not a clinical call.

CA9 p.Thr205Ile

c.614C>T · VCV4217560

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1349 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,178)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1349	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -9.81	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 1.5	GERP 0.39, phastCons 0.88
Regional constraint	o/e 0.99	unconstrained · MANE · 7,062 bp · p 0.76 · regional, not allelic
Overall
CADD	15.24	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

No allele count reported in gnomAD v4.1 (AN 1,613,178). 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: CA9
Protein: p.Thr205Ile
Coding: c.614C>T
MANE Select: NM_001216
Type: single nucleotide variant
Location: chr9:35676073 (GRCh38)
Gene constraint: LOEUF 1.021 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.13 · 32 PDB
Residue 205: a disulfide bond; a β-strand; the alpha-carbonic anhydrase domain; the 'catalytic' region

Full CA9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CA9 p.Pro114= Benign ★★ same type
CA9 p.Ala155Thr Uncertain significance ★ ⚠ same type
CA9 p.Ala176Val Uncertain significance ★ ⚠ same type
CA9 p.Ala232Val Uncertain significance ★ ⚠ same type
CA9 p.Ala300Ser Uncertain significance ★ ⚠ same type
CA9 p.Ala353Thr Uncertain significance ★ ⚠ same type
CA9 p.Ala377Glu Uncertain significance ★ ⚠ same type
CA9 p.Ala425Ser 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/ca9-p-thr205ile (accessed [today's date]).

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