Is ACMSD p.Pro11= (c.33A>T) pathogenic?

ACMSD p.Pro11= (c.33A>T) is classified Benign in ACMSD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-05-03). Low-frequency (popmax 4.38%, afr).

How common is ACMSD p.Pro11= (c.33A>T) in the general population?

ACMSD p.Pro11= (c.33A>T) is low-frequency (popmax 4.38%, afr) (gnomAD).

ACMSD p.Pro11=

c.33A>T · rs41320845 · VCV767825

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.38%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 2.3, phastCons 1
Overall
CADD	9.931	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.38% African / African-American · 3,281/74,926 alleles

Filtering AF 4.25% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.2%

Overall 0.229% 3,684/1,612,198 alleles · low-frequency exomes 1,834/1,459,906 · genomes 1,850/152,292 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.38%	23
Remaining individualsnot grpmax-eligible	0.296%	337
Admixed American	0.272%	368
Middle Eastern	0.165%	605
South Asian	0.0132%	7,571
European (non-Finnish)	0.0028%	35,718

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.Pro11=
Coding: c.33A>T
MANE Select: NM_138326
dbSNP: rs41320845
Type: single nucleotide variant
Location: chr2:134838715 (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 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
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-pro11 (accessed [today's date]).

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