Is DSPP p.Asp236= (c.708T>C) pathogenic?

DSPP p.Asp236= (c.708T>C) is classified Benign in DSPP (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-27). Common (popmax 14.9%, afr) — too common for a highly-penetrant pathogenic allele.

DSPP p.Asp236=

Q: How common is DSPP p.Asp236= (c.708T>C) in the general population?

DSPP p.Asp236= (c.708T>C) is common (popmax 14.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.708T>C · rs61731010 · VCV260358

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 14.9%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -2.4	GERP -3
Overall
CADD	1.144	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 14.9% African / African-American · 11,205/74,966 alleles

Filtering AF 14.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.6%

Overall 0.783% 12,636/1,614,036 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	14.9%	7
Admixed American	1.05%	95
Remaining individualsnot grpmax-eligible	0.963%	104
Middle Eastern	0.33%	303
South Asian	0.0406%	2,461
European (non-Finnish)	0.0119%	8,429

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: DSPP
Protein: p.Asp236=
Coding: c.708T>C
dbSNP: rs61731010
Type: single nucleotide variant
Location: chr4:87612894 (GRCh38)

Full DSPP 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/dspp-p-asp236 (accessed [today's date]).

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