Is DPCD p.Asp146His (c.436G>C) pathogenic?

DPCD p.Asp146His (c.436G>C) is classified Uncertain significance in DPCD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely benign (0.2755); Ultra-rare (popmax 0.0267%, afr).

How common is DPCD p.Asp146His (c.436G>C) in the general population?

DPCD p.Asp146His (c.436G>C) is ultra-rare (popmax 0.0267%, afr) (gnomAD).

What do computational predictors say about DPCD p.Asp146His (c.436G>C)?

AlphaMissense predicts likely benign (score 0.2755) — an in-silico prediction, not a clinical call.

DPCD p.Asp146His

c.436G>C · VCV4244347

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2755 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2755	likely benign
REVEL	0.441	indeterminate
SaProt	LLR -13.64	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.22	acceptor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 12	GERP 2.5, 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 0.0267% African / African-American · 20/74,870 alleles

Filtering AF 0.0177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.0013% 21/1,613,690 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0267%	3,743
European (non-Finnish)	8.48e-05%	1,179,940

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.Asp146His
Coding: c.436G>C
MANE Select: NM_015448
Type: single nucleotide variant
Location: chr10:101608866 (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.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
DPCD p.Arg125Cys 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-asp146his (accessed [today's date]).

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