Is CA4 p.Ser119= (c.357C>T) pathogenic?

CA4 p.Ser119= (c.357C>T) is classified Benign/Likely benign in CA4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-07-12). Rare (popmax 0.105%, eas); Associated with inherited retinal dystrophy.

What condition is associated with CA4 p.Ser119= (c.357C>T)?

CA4 p.Ser119= (c.357C>T) is associated with inherited retinal dystrophy, retinitis pigmentosa (ClinVar).

How common is CA4 p.Ser119= (c.357C>T) in the general population?

CA4 p.Ser119= (c.357C>T) is rare (popmax 0.105%, eas) (gnomAD).

CA4 p.Ser119=

c.357C>T · rs765898059 · VCV324230

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.105%, eas)

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.2	GERP -3.3
Overall
CADD	2.144	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.105% East Asian · 47/44,882 alleles

Filtering AF 0.0808% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0725%

Overall 0.00396% 64/1,614,172 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.105%	955
Remaining individualsnot grpmax-eligible	0.008%	12,502
South Asian	0.00439%	22,773
African / African-American	0.00133%	75,030
European (non-Finnish)	0.000593%	168,575

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: CA4
Protein: p.Ser119=
Coding: c.357C>T
MANE Select: NM_000717
dbSNP: rs765898059
Type: single nucleotide variant
Location: chr17:60157515 (GRCh38)
Gene constraint: LOEUF 0.975 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.86 · 10 PDB
Residue 119: a disulfide bond; the alpha-carbonic anhydrase domain

Full CA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa

Similar variants

CA4 p.Asp268Asn Uncertain significance ★★ ⚠ same condition
CA4 p.Ile54Met Uncertain significance ★★ ⚠ same condition
CA4 p.Phe70Leu Uncertain significance ★★ ⚠ same condition
CA4 c.-24G>C Benign ★★ same condition
CA4 c.-47C>G Benign ★★ same condition
CA4 p.Ala164= Benign/Likely benign ★★ same condition
CA4 p.Arg239Gln Benign ★★ same condition
CA4 p.Asn177Lys Benign/Likely 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/ca4-p-ser119 (accessed [today's date]).

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