Is SLC26A1 p.Arg287Cys (c.859C>T) pathogenic?

SLC26A1 p.Arg287Cys (c.859C>T) is classified Conflicting classifications of pathogenicity in SLC26A1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-11-08). AlphaMissense: likely benign (0.1085); Ultra-rare (popmax 0.0142%, nfe).

How common is SLC26A1 p.Arg287Cys (c.859C>T) in the general population?

SLC26A1 p.Arg287Cys (c.859C>T) is ultra-rare (popmax 0.0142%, nfe) (gnomAD).

What do computational predictors say about SLC26A1 p.Arg287Cys (c.859C>T)?

AlphaMissense predicts likely benign (score 0.1085) — an in-silico prediction, not a clinical call.

SLC26A1 p.Arg287Cys

c.859C>T · rs201572215 · VCV796315

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1085 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0142%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1085	likely benign
REVEL	0.331	indeterminate
SaProt	LLR -8.88	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.4	GERP -2.5, phastCons 0.023
Regional constraint	o/e 1.03	unconstrained · MANE · 2,867 bp · p 0.36 · regional, not allelic
Overall
CADD	22.9	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 0.0142% European (non-Finnish) · 167/1,175,304 alleles

Filtering AF 0.0124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0117%

Overall 0.0266% 425/1,599,820 alleles · ultra-rare exomes 358/1,447,456 · genomes 67/152,364 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.394%	254
European (non-Finnish)grpmax	0.0142%	7,038
Remaining individualsnot grpmax-eligible	0.0129%	7,747
African / African-American	0.0107%	9,360
South Asian	0.00675%	14,822
East Asian	0.00452%	22,115

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: SLC26A1
Protein: p.Arg287Cys
Coding: c.859C>T
MANE Select: NM_022042
dbSNP: rs201572215
Type: single nucleotide variant
Location: chr4:990080 (GRCh38)

Full SLC26A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/slc26a1-p-arg287cys (accessed [today's date]).

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