Is DPCD p.Arg125Cys (c.373C>T) pathogenic?

DPCD p.Arg125Cys (c.373C>T) is classified Uncertain significance in DPCD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-25). AlphaMissense: likely benign (0.097); Ultra-rare (popmax 0.0227%, afr).

How common is DPCD p.Arg125Cys (c.373C>T) in the general population?

DPCD p.Arg125Cys (c.373C>T) is ultra-rare (popmax 0.0227%, afr) (gnomAD).

What do computational predictors say about DPCD p.Arg125Cys (c.373C>T)?

AlphaMissense predicts likely benign (score 0.097) — an in-silico prediction, not a clinical call.

DPCD p.Arg125Cys

c.373C>T · rs144747818 · VCV2227125

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.097 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.097	likely benign
REVEL	0.458	indeterminate
SaProt	LLR -13.01	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 8,613 bp · p 0.025 · regional, not allelic
Overall
CADD	32.0	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 0.0227% African / African-American · 17/74,826 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0119%

Overall 0.00502% 81/1,613,606 alleles · ultra-rare exomes 72/1,461,798 · genomes 9/151,808 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0227%	4,402
Remaining individualsnot grpmax-eligible	0.008%	12,496
European (non-Finnish)	0.00449%	22,262
South Asian	0.00439%	22,765
Admixed American	0.00333%	29,993

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: DPCD
Protein: p.Arg125Cys
Coding: c.373C>T
MANE Select: NM_015448
dbSNP: rs144747818
Type: single nucleotide variant
Location: chr10:101601305 (GRCh38)
Gene constraint: LOEUF 1.07 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.21

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

Similar variants

DPCD p.Arg125His Uncertain significance ★ ⚠ same residue
DPCD p.Leu156Ser Benign ★★ same type
DPCD p.Ala155Pro Uncertain significance ★ ⚠ same type
DPCD p.Ala155Thr Uncertain significance ★ ⚠ same type
DPCD p.Ala193Thr Uncertain significance ★ ⚠ same type
DPCD p.Ala89Gly Uncertain significance ★ ⚠ same type
DPCD p.Ala89Thr Uncertain significance ★ ⚠ same type
DPCD p.Arg105Trp Uncertain significance ★ ⚠ same type

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/dpcd-p-arg125cys (accessed [today's date]).

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