Is SLC26A2 p.Pro82= (c.246A>G) pathogenic?

SLC26A2 p.Pro82= (c.246A>G) is classified Likely benign in SLC26A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-17). Very rare (popmax 6.19e-05%); Associated with multiple epiphyseal dysplasia type 4.

What condition is associated with SLC26A2 p.Pro82= (c.246A>G)?

SLC26A2 p.Pro82= (c.246A>G) is associated with multiple epiphyseal dysplasia type 4, diastrophic dysplasia, atelosteogenesis type II (ClinVar).

How common is SLC26A2 p.Pro82= (c.246A>G) in the general population?

SLC26A2 p.Pro82= (c.246A>G) is very rare (popmax 6.19e-05%) (gnomAD).

How is Multiple epiphyseal dysplasia type 4 inherited?

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

SLC26A2 p.Pro82=

c.246A>G · rs1755020721 · VCV1540019

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.19e-05%)

Conditions

multiple epiphyseal dysplasia type 4

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 2.7	GERP -1, phastCons 0.033
Overall
CADD	8.235	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.19e-05%

Overall 6.19e-05% 1/1,614,256 alleles · very rare exomes 1/1,461,882 · genomes 0/152,374 · joint denominator

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: SLC26A2
Protein: p.Pro82=
Coding: c.246A>G
MANE Select: NM_000112
dbSNP: rs1755020721
Type: single nucleotide variant
Location: chr5:149977898 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.97 · 4 PDB

Full SLC26A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

multiple epiphyseal dysplasia type 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: diastrophic dysplasia atelosteogenesis type II achondrogenesis type IB

For Multiple epiphyseal dysplasia type 4 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

SLC26A2 p.Pro82fs Pathogenic ★ same residue
SLC26A2 c.700-1G>C Pathogenic/Likely pathogenic ★★ same condition
SLC26A2 c.-26+2T>C Pathogenic ★★ same condition
SLC26A2 p.Ala386Val Pathogenic/Likely pathogenic ★★ same condition
SLC26A2 p.Ala715Val Pathogenic/Likely pathogenic ★★ same condition
SLC26A2 p.Arg178Ter Pathogenic ★★ same condition
SLC26A2 p.Arg279Trp Pathogenic/Likely pathogenic ★★ same condition
SLC26A2 p.Asn425Asp Pathogenic/Likely 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/slc26a2-p-pro82 (accessed [today's date]).

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