Is ADAMDEC1 p.Pro439Ser (c.1315C>T) pathogenic?

ADAMDEC1 p.Pro439Ser (c.1315C>T) is classified Benign in ADAMDEC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-12-28). AlphaMissense: likely benign (0.1078); Common (popmax 5.11%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about ADAMDEC1 p.Pro439Ser (c.1315C>T)?

AlphaMissense predicts likely benign (score 0.1078) — an in-silico prediction, not a clinical call.

ADAMDEC1 p.Pro439Ser

Q: How common is ADAMDEC1 p.Pro439Ser (c.1315C>T) in the general population?

ADAMDEC1 p.Pro439Ser (c.1315C>T) is common (popmax 5.11%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1315C>T · rs76707982 · VCV781136

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1078 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.11%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1078	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -7.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.1	GERP 0.3
Regional constraint	o/e 1.05	unconstrained · MANE · 21 kb · p 0.21 · regional, not allelic
Overall
CADD	11.25	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 5.11% African / African-American · 3,795/74,308 alleles

Filtering AF 4.97% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.92%

Overall 0.266% 4,262/1,602,072 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.11%	20
Remaining individualsnot grpmax-eligible	0.382%	262
Admixed American	0.281%	356
Middle Eastern	0.133%	753
South Asian	0.0212%	4,715
European (non-Finnish)	0.00358%	27,956

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: ADAMDEC1
Protein: p.Pro439Ser
Coding: c.1315C>T
dbSNP: rs76707982
Type: single nucleotide variant
Location: chr8:24402087 (GRCh38)

Full ADAMDEC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/adamdec1-p-pro439ser (accessed [today's date]).

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