Is AMD1 p.Arg210His (c.629G>A) pathogenic?

AMD1 p.Arg210His (c.629G>A) is classified Uncertain significance in AMD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-13). AlphaMissense: likely benign (0.1057); Ultra-rare (popmax 0.012%, afr).

How common is AMD1 p.Arg210His (c.629G>A) in the general population?

AMD1 p.Arg210His (c.629G>A) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about AMD1 p.Arg210His (c.629G>A)?

AlphaMissense predicts likely benign (score 0.1057) — an in-silico prediction, not a clinical call.

AMD1 p.Arg210His

c.629G>A · VCV4046134

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1057 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1057	likely benign
REVEL	0.225	benign-leaning
SaProt	LLR -4.05	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 8.6	GERP -0.068, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 4,672 bp · p 1.3e-09 · regional, not allelic
Overall
CADD	24.1	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 0.012% African / African-American · 9/74,690 alleles

Filtering AF 0.00625% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00469%

Overall 0.00093% 15/1,612,462 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,299
Remaining individualsnot grpmax-eligible	0.00321%	31,195
European (non-Finnish)	0.000339%	294,859

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: AMD1
Protein: p.Arg210His
Coding: c.629G>A
MANE Select: NM_001634
Type: single nucleotide variant
Location: chr6:110892748 (GRCh38)
Gene constraint: LOEUF 0.442 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 93.52 · 28 PDB
Residue 210: an α-helix

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

Similar variants

AMD1 p.Arg210Cys Uncertain significance ★ ⚠ same residue
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.Arg269Gly Uncertain significance ★ ⚠ same type
AMD1 p.Arg307His 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-arg210his (accessed [today's date]).

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