Is SLC26A3 p.Arg175Ser (c.525G>C) pathogenic?

SLC26A3 p.Arg175Ser (c.525G>C) is classified Likely pathogenic in SLC26A3 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: ambiguous (0.5535); Absent from gnomAD v4.1; Associated with congenital secretory chloride diarrhea 1.

What condition is associated with SLC26A3 p.Arg175Ser (c.525G>C)?

SLC26A3 p.Arg175Ser (c.525G>C) is associated with congenital secretory chloride diarrhea 1 (ClinVar).

How common is SLC26A3 p.Arg175Ser (c.525G>C) in the general population?

SLC26A3 p.Arg175Ser (c.525G>C) is absent from gnomAD v4.1 (gnomAD).

How is Congenital chloride diarrhea inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about SLC26A3 p.Arg175Ser (c.525G>C)?

AlphaMissense predicts ambiguous (score 0.5535) — an in-silico prediction, not a clinical call.

SLC26A3 p.Arg175Ser

c.525G>C · rs386833484 · VCV56003

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5535 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

congenital secretory chloride diarrhea 1

Computational evidence

Protein change
AlphaMissense	0.5535	ambiguous
REVEL	0.575	indeterminate
SaProt	LLR -10.43	damaging
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.55 · evaluated, not missing
Constraint at this position
Regional constraint	o/e 0.99	unconstrained · MANE · 29 kb · p 0.86 · regional, not allelic
Overall
CADD	12.31	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SLC26A3
Protein: p.Arg175Ser
Coding: c.525G>C
MANE Select: NM_000111
dbSNP: rs386833484
Type: single nucleotide variant
Location: chr7:107791093 (GRCh38)
Gene constraint: LOEUF 0.857 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.91 · 13 PDB
Residue 175: a UniProt-annotated variant site (in diar1); an α-helix

Full SLC26A3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital secretory chloride diarrhea 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital chloride diarrhea (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

SLC26A3 c.1312-1G>T Pathogenic/Likely pathogenic ★★ same condition
SLC26A3 c.1514+1G>A Pathogenic ★★ same condition
SLC26A3 c.2063-1G>T Pathogenic ★★ same condition
SLC26A3 c.571-1G>T Pathogenic ★★ same condition
SLC26A3 c.571-2A>G Pathogenic/Likely pathogenic ★★ same condition
SLC26A3 p.Ala347Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
SLC26A3 p.Arg566Ter Pathogenic ★★ same condition
SLC26A3 p.Arg579Ter Pathogenic ★★ 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/slc26a3-p-arg175ser (accessed [today's date]).

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