Is DPCD p.Leu156Ser (c.467T>C) pathogenic?

DPCD p.Leu156Ser (c.467T>C) is classified Benign in DPCD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2020-01-23). AlphaMissense: likely benign (0.0483); Common (popmax 30.4%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about DPCD p.Leu156Ser (c.467T>C)?

AlphaMissense predicts likely benign (score 0.0483) — an in-silico prediction, not a clinical call.

DPCD p.Leu156Ser

Q: How common is DPCD p.Leu156Ser (c.467T>C) in the general population?

DPCD p.Leu156Ser (c.467T>C) is common (popmax 30.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.467T>C · rs7006 · VCV1233427

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0483 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 30.4%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0483	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -8.73	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 -1.4	GERP -5
Regional constraint	o/e 0.81	unconstrained · MANE · 8,613 bp · p 0.025 · regional, not allelic
Overall
CADD	0.143	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 30.4% African / African-American · 22,783/74,866 alleles

Filtering AF 30.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 30%

Overall 27.5% 444,188/1,612,594 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	32.9%	3
African / African-Americangrpmax	30.4%	3
European (non-Finnish)	29.1%	3
Remaining individualsnot grpmax-eligible	27.9%	4
Finnishnot grpmax-eligible	25.2%	4
Middle Eastern	24.9%	4
Amishnot grpmax-eligible	23.6%	4
Admixed American	20.3%	5
South Asian	15.9%	6
East Asian	13.6%	7

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu156Ser
Coding: c.467T>C
MANE Select: NM_015448
dbSNP: rs7006
Type: single nucleotide variant
Location: chr10:101608897 (GRCh38)
Gene constraint: LOEUF 1.07 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.21
Residue 156: a UniProt-annotated variant site (in)

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

Similar variants

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
DPCD p.Arg125His 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-leu156ser (accessed [today's date]).

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