Is SLC26A2 p.Pro332= (c.996G>A) pathogenic?

SLC26A2 p.Pro332= (c.996G>A) is classified Likely benign in SLC26A2 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-10-11). Very rare (popmax 0.00439%, sas); Associated with diastrophic dysplasia.

What condition is associated with SLC26A2 p.Pro332= (c.996G>A)?

SLC26A2 p.Pro332= (c.996G>A) is associated with diastrophic dysplasia, multiple epiphyseal dysplasia type 4, atelosteogenesis type II (ClinVar).

How common is SLC26A2 p.Pro332= (c.996G>A) in the general population?

SLC26A2 p.Pro332= (c.996G>A) is very rare (popmax 0.00439%, sas) (gnomAD).

How is Diastrophic dysplasia inherited?

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

SLC26A2 p.Pro332=

c.996G>A · rs376300575 · VCV1084226

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Conditions

diastrophic dysplasia

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 -5.5	GERP -5.5
Overall
CADD	0.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,080 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000558% 9/1,614,012 alleles · very rare exomes 7/1,461,830 · genomes 2/152,182 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,770
Admixed American	0.00167%	60,004
European (non-Finnish)	0.000339%	295,005

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.Pro332=
Coding: c.996G>A
MANE Select: NM_000112
dbSNP: rs376300575
Type: single nucleotide variant
Location: chr5:149980589 (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

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

Also linked: multiple epiphyseal dysplasia type 4 atelosteogenesis type II achondrogenesis type IB

For Diastrophic dysplasia (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

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
SLC26A2 p.Cys303Ter 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-pro332 (accessed [today's date]).

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