Is ACMSD p.Ala162Val (c.485C>T) pathogenic?

ACMSD p.Ala162Val (c.485C>T) is classified Uncertain significance in ACMSD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-20). AlphaMissense: likely benign (0.1362); Ultra-rare (popmax 0.0383%, amr).

How common is ACMSD p.Ala162Val (c.485C>T) in the general population?

ACMSD p.Ala162Val (c.485C>T) is ultra-rare (popmax 0.0383%, amr) (gnomAD).

What do computational predictors say about ACMSD p.Ala162Val (c.485C>T)?

AlphaMissense predicts likely benign (score 0.1362) — an in-silico prediction, not a clinical call.

ACMSD p.Ala162Val

c.485C>T · rs148826882 · VCV2386367

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1362 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0383%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1362	likely benign
REVEL	0.238	benign-leaning
SaProt	LLR -10.50	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 0.65	GERP -2.4
Regional constraint	o/e 1.03	unconstrained · MANE · 63 kb · p 0.52 · regional, not allelic
Overall
CADD	18.19	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 0.0383% Admixed American · 23/60,010 alleles

Filtering AF 0.0261% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0222%

Overall 0.0134% 217/1,613,684 alleles · ultra-rare exomes 198/1,461,358 · genomes 19/152,326 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0383%	2,609
European (non-Finnish)	0.0153%	6,519
Remaining individualsnot grpmax-eligible	0.0128%	7,808
Finnishnot grpmax-eligible	0.00313%	31,995
African / African-American	0.00266%	37,531
South Asian	0.0011%	91,048

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.Ala162Val
Coding: c.485C>T
MANE Select: NM_138326
dbSNP: rs148826882
Type: single nucleotide variant
Location: chr2:134863630 (GRCh38)
Gene constraint: LOEUF 1.063 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.67 · 6 PDB
Residue 162: an α-helix

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.Ala223Thr Uncertain significance ★ ⚠ same type
ACMSD p.Arg109Gly 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-ala162val (accessed [today's date]).

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