Is ADAM32 p.Val448Phe (c.1342G>T) pathogenic?

ADAM32 p.Val448Phe (c.1342G>T) is classified Uncertain significance in ADAM32 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-14). AlphaMissense: likely benign (0.0873); Very rare (popmax 0.00183%, amr).

How common is ADAM32 p.Val448Phe (c.1342G>T) in the general population?

ADAM32 p.Val448Phe (c.1342G>T) is very rare (popmax 0.00183%, amr) (gnomAD).

What do computational predictors say about ADAM32 p.Val448Phe (c.1342G>T)?

AlphaMissense predicts likely benign (score 0.0873) — an in-silico prediction, not a clinical call.

ADAM32 p.Val448Phe

c.1342G>T · rs143711220 · VCV3145580

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0873 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00183%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0873	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -6.99	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 -13	GERP -4.8
Regional constraint	o/e 0.93	unconstrained · MANE · 177 kb · p 0.04 · regional, not allelic
Overall
CADD	0.006	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 0.00183% Admixed American · 1/54,746 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00035% 5/1,429,904 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00183%	54,746
European (non-Finnish)	0.000343%	291,253

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: ADAM32
Protein: p.Val448Phe
Coding: c.1342G>T
MANE Select: NM_145004
dbSNP: rs143711220
Type: single nucleotide variant
Location: chr8:39223055 (GRCh38)
Gene constraint: LOEUF 1.041 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.71
Residue 448: the disintegrin domain

Full ADAM32 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADAM32 p.Val448Ile Uncertain significance ★ ⚠ same residue
ADAM32 p.Arg298His Likely benign ★★ ⚠ same type
ADAM32 p.Ala154Thr Uncertain significance ★ ⚠ same type
ADAM32 p.Ala179Ser Uncertain significance ★ ⚠ same type
ADAM32 p.Ala621Val Uncertain significance ★ ⚠ same type
ADAM32 p.Ala699Thr Uncertain significance ★ ⚠ same type
ADAM32 p.Arg284His Uncertain significance ★ ⚠ same type
ADAM32 p.Arg501Cys 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/adam32-p-val448phe (accessed [today's date]).

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