Is SLC26A1 p.Ser415Phe (c.1244C>T) pathogenic?

SLC26A1 p.Ser415Phe (c.1244C>T) is classified Uncertain significance in SLC26A1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-13). AlphaMissense: likely pathogenic (0.8947); Rare (popmax 0.136%, mid); Associated with hypersulfaturia.

What condition is associated with SLC26A1 p.Ser415Phe (c.1244C>T)?

SLC26A1 p.Ser415Phe (c.1244C>T) is associated with hypersulfaturia, nephrolithiasis susceptibility caused by SLC26A1 (ClinVar).

How common is SLC26A1 p.Ser415Phe (c.1244C>T) in the general population?

SLC26A1 p.Ser415Phe (c.1244C>T) is rare (popmax 0.136%, mid) (gnomAD).

What do computational predictors say about SLC26A1 p.Ser415Phe (c.1244C>T)?

AlphaMissense predicts likely pathogenic (score 0.8947) — an in-silico prediction, not a clinical call.

SLC26A1 p.Ser415Phe

c.1244C>T · rs200470975 · VCV860198

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.8947 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.136%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hypersulfaturia

⚠ 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	0.8947	likely pathogenic
REVEL	0.951	strongly pathogenic-leaning
SaProt	LLR -12.87	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 2,867 bp · p 0.36 · regional, not allelic
Overall
CADD	27.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.136% Middle Eastern · 8/5,862 alleles

Filtering AF 0.0679% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.051%

Overall 0.0461% 721/1,562,362 alleles · rare exomes 662/1,409,994 · genomes 59/152,368 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.136%	733
European (non-Finnish)	0.0561%	1,784
Remaining individualsnot grpmax-eligible	0.0512%	1,954
Admixed American	0.0307%	3,254
Ashkenazi Jewishnot grpmax-eligible	0.0244%	4,105
African / African-American	0.0108%	9,261
South Asian	0.00353%	28,366
East Asian	0.00237%	42,162

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.Ser415Phe
Coding: c.1244C>T
MANE Select: NM_022042
dbSNP: rs200470975
Type: single nucleotide variant
Location: chr4:989695 (GRCh38)

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

Disease context

hypersulfaturia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: nephrolithiasis susceptibility caused by SLC26A1

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-ser415phe (accessed [today's date]).

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