Is DPCD p.Tyr116Cys (c.347A>G) pathogenic?

DPCD p.Tyr116Cys (c.347A>G) is classified Uncertain significance in DPCD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-04). AlphaMissense: ambiguous (0.5637); Ultra-rare (popmax 0.0121%, sas).

How common is DPCD p.Tyr116Cys (c.347A>G) in the general population?

DPCD p.Tyr116Cys (c.347A>G) is ultra-rare (popmax 0.0121%, sas) (gnomAD).

What do computational predictors say about DPCD p.Tyr116Cys (c.347A>G)?

AlphaMissense predicts ambiguous (score 0.5637) — an in-silico prediction, not a clinical call.

DPCD p.Tyr116Cys

c.347A>G · VCV4014503

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5637 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, sas)

Computational evidence

Protein change
AlphaMissense	0.5637	ambiguous
REVEL	0.444	indeterminate
SaProt	LLR -14.38	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 2.6, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 8,613 bp · p 0.025 · regional, not allelic
Overall
CADD	25.9	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 0.0121% South Asian · 11/91,054 alleles

Filtering AF 0.00677% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00522%

Overall 0.00137% 20/1,461,856 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0121%	8,278
Finnishnot grpmax-eligible	0.00312%	32,008
Admixed American	0.00167%	60,014
European (non-Finnish)	0.000509%	196,648

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.Tyr116Cys
Coding: c.347A>G
MANE Select: NM_015448
Type: single nucleotide variant
Location: chr10:101601279 (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-tyr116cys (accessed [today's date]).

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