Is DSPP p.Ala177Thr (c.529G>A) pathogenic?

DSPP p.Ala177Thr (c.529G>A) is classified Conflicting classifications of pathogenicity in DSPP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-07-08). AlphaMissense: likely benign (0.0582); Ultra-rare (popmax 0.036%, afr).

How common is DSPP p.Ala177Thr (c.529G>A) in the general population?

DSPP p.Ala177Thr (c.529G>A) is ultra-rare (popmax 0.036%, afr) (gnomAD).

What do computational predictors say about DSPP p.Ala177Thr (c.529G>A)?

AlphaMissense predicts likely benign (score 0.0582) — an in-silico prediction, not a clinical call.

DSPP p.Ala177Thr

c.529G>A · rs374609929 · VCV2883023

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0582 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.036%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0582	likely benign
REVEL	0.131	moderately benign-leaning
SaProt	LLR -5.93	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.29	GERP -3.7
Regional constraint	o/e 0.98	unconstrained · MANE · 3,360 bp · p 0.63 · regional, not allelic
Overall
CADD	0.243	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 0.036% African / African-American · 27/74,896 alleles

Filtering AF 0.0254% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0219%

Overall 0.00347% 56/1,614,006 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.036%	2,774
Middle Eastern	0.0164%	6,084
Admixed American	0.01%	10,001
Remaining individualsnot grpmax-eligible	0.0064%	15,622
East Asian	0.00223%	44,902
South Asian	0.0022%	45,537
European (non-Finnish)	0.00127%	78,668

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.Ala177Thr
Coding: c.529G>A
dbSNP: rs374609929
Type: single nucleotide variant
Location: chr4:87612715 (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-ala177thr (accessed [today's date]).

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