Is ADAM29 p.Ile55Phe (c.163A>T) pathogenic?

ADAM29 p.Ile55Phe (c.163A>T) is classified Uncertain significance in ADAM29 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). AlphaMissense: likely benign (0.1251); Ultra-rare (popmax 0.049%, eas).

How common is ADAM29 p.Ile55Phe (c.163A>T) in the general population?

ADAM29 p.Ile55Phe (c.163A>T) is ultra-rare (popmax 0.049%, eas) (gnomAD).

What do computational predictors say about ADAM29 p.Ile55Phe (c.163A>T)?

AlphaMissense predicts likely benign (score 0.1251) — an in-silico prediction, not a clinical call.

ADAM29 p.Ile55Phe

c.163A>T · VCV4005254

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1251 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.049%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1251	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -8.13	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 1.8	GERP -0.32, phastCons 0.013
Regional constraint	o/e 0.97	unconstrained · MANE · 2,459 bp · p 0.3 · regional, not allelic
Overall
CADD	13.29	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 0.049% East Asian · 22/44,888 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0279%

Overall 0.00136% 22/1,612,464 alleles · ultra-rare

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: ADAM29
Protein: p.Ile55Phe
Coding: c.163A>T
MANE Select: NM_014269
Type: single nucleotide variant
Location: chr4:174975688 (GRCh38)
Gene constraint: LOEUF 1.939 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.07

Full ADAM29 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADAM29 p.Ala314Glu Uncertain significance ★ ⚠ same type
ADAM29 p.Ala88Val Uncertain significance ★ ⚠ same type
ADAM29 p.Arg213Cys Uncertain significance ★ ⚠ same type
ADAM29 p.Arg311His Uncertain significance ★ ⚠ same type
ADAM29 p.Arg501His Uncertain significance ★ ⚠ same type
ADAM29 p.Arg530Cys Uncertain significance ★ ⚠ same type
ADAM29 p.Arg723Cys Uncertain significance ★ ⚠ same type
ADAM29 p.Arg804Thr 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/adam29-p-ile55phe (accessed [today's date]).

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