Is CA8 p.Ser71Phe (c.212C>T) pathogenic?

CA8 p.Ser71Phe (c.212C>T) is classified Uncertain significance in CA8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-07). AlphaMissense: likely benign (0.1691); Ultra-rare (popmax 0.0132%, sas); Associated with Inborn genetic diseases.

What condition is associated with CA8 p.Ser71Phe (c.212C>T)?

CA8 p.Ser71Phe (c.212C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CA8 p.Ser71Phe (c.212C>T) in the general population?

CA8 p.Ser71Phe (c.212C>T) is ultra-rare (popmax 0.0132%, sas) (gnomAD).

What do computational predictors say about CA8 p.Ser71Phe (c.212C>T)?

AlphaMissense predicts likely benign (score 0.1691) — an in-silico prediction, not a clinical call.

CA8 p.Ser71Phe

c.212C>T · rs773560890 · VCV3136152

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1691 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1691	likely benign
REVEL	0.446	indeterminate
SaProt	LLR -7.77	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 15 kb · p 0.24 · regional, not allelic
Overall
CADD	26.2	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 0.0132% South Asian · 12/91,078 alleles

Filtering AF 0.00751% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00593%

Overall 0.000821% 12/1,461,884 alleles · ultra-rare

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.Ser71Phe
Coding: c.212C>T
MANE Select: NM_004056
dbSNP: rs773560890
Type: single nucleotide variant
Location: chr8:60279769 (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 71: 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 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
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-ser71phe (accessed [today's date]).

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