Is DSPP p.Pro231Thr (c.691C>A) pathogenic?

DSPP p.Pro231Thr (c.691C>A) is classified Benign in DSPP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.069); Low-frequency (popmax 2.94%, afr).

How common is DSPP p.Pro231Thr (c.691C>A) in the general population?

DSPP p.Pro231Thr (c.691C>A) is low-frequency (popmax 2.94%, afr) (gnomAD).

What do computational predictors say about DSPP p.Pro231Thr (c.691C>A)?

AlphaMissense predicts likely benign (score 0.069) — an in-silico prediction, not a clinical call.

DSPP p.Pro231Thr

c.691C>A · rs61738509 · VCV783423

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.069 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.94%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.069	likely benign
REVEL	0.131	moderately benign-leaning
SaProt	LLR -5.28	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.41	GERP -1.3
Regional constraint	o/e 0.98	unconstrained · MANE · 3,360 bp · p 0.63 · regional, not allelic
Overall
CADD	13.71	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 2.94% African / African-American · 2,203/75,024 alleles

Filtering AF 2.83% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.79%

Overall 0.292% 4,719/1,614,108 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.94%	34
Middle Eastern	2%	50
South Asian	0.516%	194
Remaining individualsnot grpmax-eligible	0.49%	204
Admixed American	0.342%	293
Ashkenazi Jewishnot grpmax-eligible	0.318%	315
European (non-Finnish)	0.11%	913
Finnishnot grpmax-eligible	0.0406%	2,462
East Asian	0.00223%	44,888

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.Pro231Thr
Coding: c.691C>A
dbSNP: rs61738509
Type: single nucleotide variant
Location: chr4:87612877 (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-pro231thr (accessed [today's date]).

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