Is ADAMDEC1 p.Ser331Phe (c.992C>T) pathogenic?

ADAMDEC1 p.Ser331Phe (c.992C>T) is classified Uncertain significance in ADAMDEC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: likely benign (0.1314); Ultra-rare (popmax 0.02%, afr).

How common is ADAMDEC1 p.Ser331Phe (c.992C>T) in the general population?

ADAMDEC1 p.Ser331Phe (c.992C>T) is ultra-rare (popmax 0.02%, afr) (gnomAD).

What do computational predictors say about ADAMDEC1 p.Ser331Phe (c.992C>T)?

AlphaMissense predicts likely benign (score 0.1314) — an in-silico prediction, not a clinical call.

ADAMDEC1 p.Ser331Phe

c.992C>T · VCV4227716

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1314 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1314	likely benign
REVEL	0.186	benign-leaning
SaProt	LLR -8.05	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.46	loss · gain 0.00 · independent
Constraint at this position
Conservation	phyloP 0.23	GERP 1.3
Regional constraint	o/e 1.05	unconstrained · MANE · 21 kb · p 0.21 · regional, not allelic
Overall
CADD	16.06	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 0.02% African / African-American · 15/74,862 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0099%

Overall 0.000992% 16/1,613,640 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.02%	4,991
Remaining individualsnot grpmax-eligible	0.0016%	62,468

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.Ser331Phe
Coding: c.992C>T
Type: single nucleotide variant
Location: chr8:24399455 (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-ser331phe (accessed [today's date]).

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