Is CA5A p.Ser242Leu (c.725C>T) pathogenic?

CA5A p.Ser242Leu (c.725C>T) is classified Uncertain significance in CA5A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). AlphaMissense: likely benign (0.3082); Very rare (popmax 0.00465%, sas); Associated with Inborn genetic diseases.

What condition is associated with CA5A p.Ser242Leu (c.725C>T)?

CA5A p.Ser242Leu (c.725C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CA5A p.Ser242Leu (c.725C>T) in the general population?

CA5A p.Ser242Leu (c.725C>T) is very rare (popmax 0.00465%, sas) (gnomAD).

What do computational predictors say about CA5A p.Ser242Leu (c.725C>T)?

AlphaMissense predicts likely benign (score 0.3082) — an in-silico prediction, not a clinical call.

CA5A p.Ser242Leu

c.725C>T · rs762793426 · VCV3136135

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3082 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00465%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3082	likely benign
REVEL	0.559	indeterminate
SaProt	LLR -12.58	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP -0.43, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 48 kb · p 0.027 · regional, not allelic
Overall
CADD	27.6	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 0.00465% South Asian · 4/85,994 alleles

Filtering AF 0.00159% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000932%

Overall 0.00101% 16/1,579,714 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00465%	21,498
East Asian	0.00239%	41,768
African / African-American	0.00137%	72,762
European (non-Finnish)	0.000858%	116,600

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: CA5A
Protein: p.Ser242Leu
Coding: c.725C>T
MANE Select: NM_001739
dbSNP: rs762793426
Type: single nucleotide variant
Location: chr16:87891848 (GRCh38)
Gene constraint: LOEUF 1.257 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.38
Residue 242: the alpha-carbonic anhydrase domain

Full CA5A 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

CA5A p.Ser242= Likely benign ★ same residue
CA5A p.Ala149Thr Uncertain significance ★★ ⚠ same condition
CA5A p.His143Asp Uncertain significance ★★ ⚠ same condition
CA5A p.Leu259Val Uncertain significance ★★ ⚠ same condition
CA5A p.Phe215Ile Uncertain significance ★★ ⚠ same condition
CA5A p.Pro222Ser Uncertain significance ★★ ⚠ same condition
CA5A p.Pro30Arg Uncertain significance ★★ ⚠ same condition
CA5A p.Thr192Met Uncertain significance ★★ ⚠ 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/ca5a-p-ser242leu (accessed [today's date]).

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