Is DPCD p.Arg125His (c.374G>A) pathogenic?

DPCD p.Arg125His (c.374G>A) is classified Uncertain significance in DPCD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-26). AlphaMissense: likely benign (0.0671); Very rare (popmax 0.00329%, sas).

How common is DPCD p.Arg125His (c.374G>A) in the general population?

DPCD p.Arg125His (c.374G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about DPCD p.Arg125His (c.374G>A)?

AlphaMissense predicts likely benign (score 0.0671) — an in-silico prediction, not a clinical call.

DPCD p.Arg125His

c.374G>A · rs757346528 · VCV2387138

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0671 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0671	likely benign
REVEL	0.242	benign-leaning
SaProt	LLR -10.65	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.3	GERP 1.6, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 8,613 bp · p 0.025 · regional, not allelic
Overall
CADD	28.5	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 0.00329% South Asian · 3/91,064 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00223% 36/1,613,694 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,355
European (non-Finnish)	0.00254%	39,330
East Asian	0.00223%	44,802
Remaining individualsnot grpmax-eligible	0.0016%	62,478
African / African-American	0.00134%	74,860

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.Arg125His
Coding: c.374G>A
MANE Select: NM_015448
dbSNP: rs757346528
Type: single nucleotide variant
Location: chr10:101601306 (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.Arg125Cys 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-arg125his (accessed [today's date]).

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