Is DSPP p.Asp243Asn (c.727G>A) pathogenic?

DSPP p.Asp243Asn (c.727G>A) is classified Benign in DSPP (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.077); Common (popmax 31.9%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about DSPP p.Asp243Asn (c.727G>A)?

AlphaMissense predicts likely benign (score 0.077) — an in-silico prediction, not a clinical call.

DSPP p.Asp243Asn

Q: How common is DSPP p.Asp243Asn (c.727G>A) in the general population?

DSPP p.Asp243Asn (c.727G>A) is common (popmax 31.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.727G>A · rs3750025 · VCV197292

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.077 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 31.9%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.077	likely benign
REVEL	0.339	indeterminate
SaProt	LLR -5.51	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.5	GERP -0.21, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 3,360 bp · p 0.63 · regional, not allelic
Overall
CADD	19.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 31.9% East Asian · 14,327/44,866 alleles

Filtering AF 31.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 31.3%

Overall 3.25% 52,520/1,614,080 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	31.9%	3
Admixed American	7.45%	13
Remaining individualsnot grpmax-eligible	4.57%	22
South Asian	4.25%	24
Ashkenazi Jewishnot grpmax-eligible	2.57%	39
African / African-American	2.32%	43
Finnishnot grpmax-eligible	2.21%	45
European (non-Finnish)	1.95%	51
Middle Eastern	1.83%	55
Amishnot grpmax-eligible	0.219%	456

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.Asp243Asn
Coding: c.727G>A
dbSNP: rs3750025
Type: single nucleotide variant
Location: chr4:87612913 (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-asp243asn (accessed [today's date]).

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