Is ADAMDEC1 p.Val172Phe (c.514G>T) pathogenic?

ADAMDEC1 p.Val172Phe (c.514G>T) is classified Uncertain significance in ADAMDEC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). AlphaMissense: likely benign (0.2092); Ultra-rare (popmax 0.0233%, amr).

How common is ADAMDEC1 p.Val172Phe (c.514G>T) in the general population?

ADAMDEC1 p.Val172Phe (c.514G>T) is ultra-rare (popmax 0.0233%, amr) (gnomAD).

What do computational predictors say about ADAMDEC1 p.Val172Phe (c.514G>T)?

AlphaMissense predicts likely benign (score 0.2092) — an in-silico prediction, not a clinical call.

ADAMDEC1 p.Val172Phe

c.514G>T · rs200134300 · VCV2589363

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2092 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0233%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2092	likely benign
REVEL	0.14	moderately benign-leaning
SaProt	LLR -11.00	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.61	GERP -3.8
Regional constraint	o/e 1.05	unconstrained · MANE · 21 kb · p 0.21 · regional, not allelic
Overall
CADD	14.62	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 0.0233% Admixed American · 14/60,006 alleles

Filtering AF 0.0194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0185%

Overall 0.0176% 284/1,613,982 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0233%	4,286
European (non-Finnish)	0.0216%	4,627
Remaining individualsnot grpmax-eligible	0.0176%	5,682
African / African-American	0.00267%	37,502
East Asian	0.00223%	44,858
Finnishnot grpmax-eligible	0.00156%	64,002

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.Val172Phe
Coding: c.514G>T
dbSNP: rs200134300
Type: single nucleotide variant
Location: chr8:24397343 (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-val172phe (accessed [today's date]).

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