Is DSPP p.Arg354His (c.1061G>A) pathogenic?

DSPP p.Arg354His (c.1061G>A) is classified Uncertain significance in DSPP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-24). AlphaMissense: likely benign (0.1155); Very rare (popmax 0.00549%, sas); Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Arg354His (c.1061G>A)?

DSPP p.Arg354His (c.1061G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Arg354His (c.1061G>A) in the general population?

DSPP p.Arg354His (c.1061G>A) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about DSPP p.Arg354His (c.1061G>A)?

AlphaMissense predicts likely benign (score 0.1155) — an in-silico prediction, not a clinical call.

DSPP p.Arg354His

c.1061G>A · rs773490979 · VCV1313932

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1155 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1155	likely benign
REVEL	0.195	benign-leaning
SaProt	LLR -6.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.71	GERP -2.6, phastCons 0.004
Regional constraint	o/e 0.98	unconstrained · MANE · 3,360 bp · p 0.63 · regional, not allelic
Overall
CADD	4.408	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,056 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00112% 18/1,613,626 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,211
East Asian	0.00223%	44,892
Admixed American	0.00167%	59,986
African / African-American	0.00134%	74,904
European (non-Finnish)	0.000847%	118,000

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.Arg354His
Coding: c.1061G>A
dbSNP: rs773490979
Type: single nucleotide variant
Location: chr4:87613247 (GRCh38)

Full DSPP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-arg354his (accessed [today's date]).

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