Is ADD3 p.Ile94Met (c.282T>G) pathogenic?

ADD3 p.Ile94Met (c.282T>G) is classified Uncertain significance in ADD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-03). AlphaMissense: ambiguous (0.4463); Ultra-rare (popmax 0.05%, amr).

How common is ADD3 p.Ile94Met (c.282T>G) in the general population?

ADD3 p.Ile94Met (c.282T>G) is ultra-rare (popmax 0.05%, amr) (gnomAD).

What do computational predictors say about ADD3 p.Ile94Met (c.282T>G)?

AlphaMissense predicts ambiguous (score 0.4463) — an in-silico prediction, not a clinical call.

ADD3 p.Ile94Met

c.282T>G · rs777179853 · VCV1396661

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4463 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.05%, amr)

Computational evidence

Protein change
AlphaMissense	0.4463	ambiguous
REVEL	0.34	indeterminate
SaProt	LLR -6.86	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.92	GERP 0.57, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 33 kb · p 0.53 · regional, not allelic
Overall
CADD	22.0	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 0.05% Admixed American · 30/60,022 alleles

Filtering AF 0.0359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0312%

Overall 0.00204% 33/1,614,154 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.05%	2,001
Finnishnot grpmax-eligible	0.00312%	32,019
South Asian	0.0011%	91,082

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: ADD3
Protein: p.Ile94Met
Coding: c.282T>G
MANE Select: NM_016824
dbSNP: rs777179853
Type: single nucleotide variant
Location: chr10:110112863 (GRCh38)
Gene constraint: LOEUF 0.395 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.83

Full ADD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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ADD3 c.1733-1G>A Uncertain significance ★★ same type
ADD3 p.Ala588Gly Uncertain significance ★★ ⚠ same type
ADD3 p.Arg27Cys Uncertain significance ★★ ⚠ same type
ADD3 p.Arg46Gln Uncertain significance ★★ ⚠ same type
ADD3 p.Arg571His Uncertain significance ★★ ⚠ same type
ADD3 p.Arg645Gln Uncertain significance ★★ ⚠ same type
ADD3 p.Asn312Asp 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/add3-p-ile94met (accessed [today's date]).

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