Is SLC26A2 p.Pro549= (c.1647A>G) pathogenic?

SLC26A2 p.Pro549= (c.1647A>G) is classified Benign/Likely benign in SLC26A2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-24). Rare (popmax 0.769%, sas); Associated with connective tissue disorder.

What condition is associated with SLC26A2 p.Pro549= (c.1647A>G)?

SLC26A2 p.Pro549= (c.1647A>G) is associated with connective tissue disorder, diastrophic dysplasia, multiple epiphyseal dysplasia type 4 (ClinVar).

How common is SLC26A2 p.Pro549= (c.1647A>G) in the general population?

SLC26A2 p.Pro549= (c.1647A>G) is rare (popmax 0.769%, sas) (gnomAD).

SLC26A2 p.Pro549=

c.1647A>G · rs200694484 · VCV788309

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.769%, sas)

Conditions

connective tissue disorder

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 0.48	GERP -1.9, phastCons 0.41
Overall
CADD	7.241	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.769% South Asian · 700/91,084 alleles

Filtering AF 0.721% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.702%

Overall 0.0462% 745/1,614,190 alleles · rare exomes 716/1,461,854 · genomes 29/152,336 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.769%	130
Remaining individualsnot grpmax-eligible	0.064%	1,563
Middle Eastern	0.033%	3,030
Admixed American	0.00333%	30,012
European (non-Finnish)	8.47e-05%	1,180,011

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.Pro549=
Coding: c.1647A>G
MANE Select: NM_000112
dbSNP: rs200694484
Type: single nucleotide variant
Location: chr5:149981240 (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

connective tissue disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

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-pro549 (accessed [today's date]).

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