Is ACHE p.Arg34Gln (c.101G>A) pathogenic?

ACHE p.Arg34Gln (c.101G>A) is classified Benign in ACHE (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0734); Low-frequency (popmax 2.66%, afr).

How common is ACHE p.Arg34Gln (c.101G>A) in the general population?

ACHE p.Arg34Gln (c.101G>A) is low-frequency (popmax 2.66%, afr) (gnomAD).

What do computational predictors say about ACHE p.Arg34Gln (c.101G>A)?

AlphaMissense predicts likely benign (score 0.0734) — an in-silico prediction, not a clinical call.

ACHE p.Arg34Gln

c.101G>A · rs17881553 · VCV785228

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0734 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.66%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0734	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -5.85	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 -2.1
Regional constraint	o/e 1.13	unconstrained · MANE · 176 bp · p 0.25 · regional, not allelic
Overall
CADD	1.247	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 2.66% African / African-American · 1,903/71,534 alleles

Filtering AF 2.56% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.52%

Overall 0.157% 2,343/1,490,604 alleles · low-frequency exomes 1,143/1,338,334 · genomes 1,200/152,270 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.66%	38
Middle Eastern	0.687%	146
Admixed American	0.198%	504
Remaining individualsnot grpmax-eligible	0.195%	513
Ashkenazi Jewishnot grpmax-eligible	0.0947%	1,056
European (non-Finnish)	0.0156%	6,430
South Asian	0.0135%	7,387

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: ACHE
Protein: p.Arg34Gln
Coding: c.101G>A
MANE Select: NM_000665
dbSNP: rs17881553
Type: single nucleotide variant
Location: chr7:100894132 (GRCh38)
Gene constraint: LOEUF 0.546 · pLI 0.81 (gnomAD)
Structure: AlphaFold pLDDT 93.04 · 81 PDB
Residue 34: a UniProt-annotated variant site (in)

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

Similar variants

ACHE p.Glu344= Benign/Likely benign ★★ same type
ACHE p.Gly89Glu Benign ★★ ⚠ same type
ACHE p.Pro135Ala Likely benign ★★ ⚠ same type
ACHE p.Pro441= Likely benign ★★ same type
ACHE p.Thr269= Benign/Likely benign ★★ same type
ACHE p.Ala14Thr Uncertain significance ★ ⚠ same type
ACHE p.Ala256Thr Uncertain significance ★ ⚠ same type
ACHE p.Ala408Gly 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/ache-p-arg34gln (accessed [today's date]).

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