Is A2ML1 p.Glu67Val (c.200A>T) pathogenic?

A2ML1 p.Glu67Val (c.200A>T) is classified Benign in A2ML1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.1574); Low-frequency (popmax 2.04%, amr).

How common is A2ML1 p.Glu67Val (c.200A>T) in the general population?

A2ML1 p.Glu67Val (c.200A>T) is low-frequency (popmax 2.04%, amr) (gnomAD).

What do computational predictors say about A2ML1 p.Glu67Val (c.200A>T)?

AlphaMissense predicts likely benign (score 0.1574) — an in-silico prediction, not a clinical call.

A2ML1 p.Glu67Val

c.200A>T · rs190479708 · VCV241887

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1574 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.04%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1574	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -8.70	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 52 kb · p 0.02 · regional, not allelic
Overall
CADD	20.5	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 2.04% Admixed American · 1,226/60,020 alleles

Filtering AF 1.95% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.91%

Overall 0.079% 1,275/1,614,182 alleles · low-frequency

Ancestry group	Frequency	1 in
Admixed Americangrpmax	2.04%	49
Remaining individualsnot grpmax-eligible	0.04%	2,500
African / African-American	0.024%	4,169
European (non-Finnish)	0.000508%	196,670

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: A2ML1
Protein: p.Glu67Val
Coding: c.200A>T
dbSNP: rs190479708
Type: single nucleotide variant
Location: chr12:8823319 (GRCh38)

Full A2ML1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/a2ml1-p-glu67val (accessed [today's date]).

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