Is DSPP p.Ser338Arg (c.1014C>A) pathogenic?

DSPP p.Ser338Arg (c.1014C>A) is classified Conflicting classifications of pathogenicity in DSPP (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-11-05). AlphaMissense: likely benign (0.3346); Ultra-rare (popmax 0.0312%, eas); Associated with Inborn genetic diseases.

What condition is associated with DSPP p.Ser338Arg (c.1014C>A)?

DSPP p.Ser338Arg (c.1014C>A) is associated with Inborn genetic diseases (ClinVar).

How common is DSPP p.Ser338Arg (c.1014C>A) in the general population?

DSPP p.Ser338Arg (c.1014C>A) is ultra-rare (popmax 0.0312%, eas) (gnomAD).

What do computational predictors say about DSPP p.Ser338Arg (c.1014C>A)?

AlphaMissense predicts likely benign (score 0.3346) — an in-silico prediction, not a clinical call.

DSPP p.Ser338Arg

c.1014C>A · rs370261412 · VCV1210961

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.3346 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0312%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3346	likely benign
REVEL	0.335	indeterminate
SaProt	LLR -7.41	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 -0.25	GERP -1.3
Regional constraint	o/e 0.98	unconstrained · MANE · 3,360 bp · p 0.63 · regional, not allelic
Overall
CADD	16.22	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 0.0312% East Asian · 14/44,880 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.00459% 74/1,613,874 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0832%	1,202
East Asiangrpmax	0.0312%	3,206
Admixed American	0.00333%	29,998
African / African-American	0.00267%	37,505
South Asian	0.0011%	91,034
European (non-Finnish)	0.000254%	393,329

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser338Arg
Coding: c.1014C>A
dbSNP: rs370261412
Type: single nucleotide variant
Location: chr4:87613200 (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-ser338arg (accessed [today's date]).

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