Is AMD1 p.Gln333Glu (c.997C>G) pathogenic?

AMD1 p.Gln333Glu (c.997C>G) is classified Uncertain significance in AMD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-07). AlphaMissense: likely benign (0.0787); Absent from gnomAD v4.1.

How common is AMD1 p.Gln333Glu (c.997C>G) in the general population?

AMD1 p.Gln333Glu (c.997C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AMD1 p.Gln333Glu (c.997C>G)?

AlphaMissense predicts likely benign (score 0.0787) — an in-silico prediction, not a clinical call.

AMD1 p.Gln333Glu

c.997C>G · VCV4046123

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0787 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0787	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -7.34	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 4.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 4,672 bp · p 1.3e-09 · regional, not allelic
Overall
CADD	18.29	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AMD1
Protein: p.Gln333Glu
Coding: c.997C>G
MANE Select: NM_001634
Type: single nucleotide variant
Location: chr6:110893608 (GRCh38)
Gene constraint: LOEUF 0.442 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 93.52 · 28 PDB

Full AMD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDK19 p.Thr31Asn Pathogenic/Likely pathogenic ★★ same type
CDK19 p.Gly28Ala Likely pathogenic ★ same type
CDK19 p.Gly28Arg Pathogenic ★ same type
CDK19 p.Tyr32His Pathogenic ★ same type
AMD1 p.Arg168Gln Uncertain significance ★ ⚠ same type
AMD1 p.Arg210Cys Uncertain significance ★ ⚠ same type
AMD1 p.Arg210His Uncertain significance ★ ⚠ same type
AMD1 p.Arg269Gly 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/amd1-p-gln333glu (accessed [today's date]).

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