Is AMD1 p.Lys56Arg (c.167A>G) pathogenic?

AMD1 p.Lys56Arg (c.167A>G) is classified Uncertain significance in AMD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-24). AlphaMissense: likely benign (0.0717); Absent from gnomAD v4.1.

How common is AMD1 p.Lys56Arg (c.167A>G) in the general population?

AMD1 p.Lys56Arg (c.167A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AMD1 p.Lys56Arg (c.167A>G)?

AlphaMissense predicts likely benign (score 0.0717) — an in-silico prediction, not a clinical call.

AMD1 p.Lys56Arg

c.167A>G · VCV4046145

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0717 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,608,798)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0717	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	LLR -7.00	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 9.3	GERP 1.9, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 12 kb · p 0.024 · regional, not allelic
Overall
CADD	22.0	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

No allele count reported in gnomAD v4.1 (AN 1,608,798). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AMD1
Protein: p.Lys56Arg
Coding: c.167A>G
MANE Select: NM_001634
Type: single nucleotide variant
Location: chr6:110887561 (GRCh38)
Gene constraint: LOEUF 0.442 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 93.52 · 28 PDB
Residue 56: a β-strand

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-lys56arg (accessed [today's date]).

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