Is DPCD p.Thr4Met (c.11C>T) pathogenic?

DPCD p.Thr4Met (c.11C>T) is classified Uncertain significance in DPCD (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely benign (0.1443); Very rare (popmax 0.0034%, amr).

How common is DPCD p.Thr4Met (c.11C>T) in the general population?

DPCD p.Thr4Met (c.11C>T) is very rare (popmax 0.0034%, amr) (gnomAD).

What do computational predictors say about DPCD p.Thr4Met (c.11C>T)?

AlphaMissense predicts likely benign (score 0.1443) — an in-silico prediction, not a clinical call.

DPCD p.Thr4Met

c.11C>T · rs386352299 · VCV91991

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1443 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0034%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1443	likely benign
REVEL	0.12	moderately benign-leaning
SaProt	LLR -7.68	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 2.2, phastCons 0.97
Regional constraint	o/e 1.43	unconstrained · MANE · 6,337 bp · p 0.013 · regional, not allelic
Overall
CADD	23.4	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 0.0034% Admixed American · 2/58,784 alleles

Filtering AF 0.000564% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.0005% 8/1,598,940 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0034%	29,392
European (non-Finnish)	0.000512%	195,142

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.Thr4Met
Coding: c.11C>T
MANE Select: NM_015448
dbSNP: rs386352299
Type: single nucleotide variant
Location: chr10:101588347 (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-thr4met (accessed [today's date]).

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