Is ACMSD p.Asp312Glu (c.936T>A) pathogenic?

ACMSD p.Asp312Glu (c.936T>A) is classified Uncertain significance in ACMSD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: likely benign (0.2162); Very rare (popmax 0.00532%, amr).

How common is ACMSD p.Asp312Glu (c.936T>A) in the general population?

ACMSD p.Asp312Glu (c.936T>A) is very rare (popmax 0.00532%, amr) (gnomAD).

What do computational predictors say about ACMSD p.Asp312Glu (c.936T>A)?

AlphaMissense predicts likely benign (score 0.2162) — an in-silico prediction, not a clinical call.

ACMSD p.Asp312Glu

c.936T>A · VCV4216222

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2162 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00532%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2162	likely benign
REVEL	0.188	benign-leaning
SaProt	LLR -10.72	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.17	GERP -0.43, phastCons 0.99
Regional constraint	o/e 1.03	unconstrained · MANE · 63 kb · p 0.52 · regional, not allelic
Overall
CADD	17.62	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 0.00532% Admixed American · 3/56,350 alleles

Filtering AF 0.00141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000692%

Overall 0.000188% 3/1,595,394 alleles · very rare

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: ACMSD
Protein: p.Asp312Glu
Coding: c.936T>A
MANE Select: NM_138326
Type: single nucleotide variant
Location: chr2:134898427 (GRCh38)
Gene constraint: LOEUF 1.063 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.67 · 6 PDB

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

Similar variants

ACMSD p.Pro11= Benign ★★ same type
ACMSD c.677-14G>T Uncertain significance ★ same type
ACMSD c.948+1G>A Uncertain significance ★ same type
ACMSD p.Ala101Thr Uncertain significance ★ ⚠ same type
ACMSD p.Ala121Val Uncertain significance ★ ⚠ same type
ACMSD p.Ala154Val Uncertain significance ★ ⚠ same type
ACMSD p.Ala162Val Uncertain significance ★ ⚠ same type
ACMSD p.Ala223Thr 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/acmsd-p-asp312glu (accessed [today's date]).

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