Is ARMC2 p.Gln52Pro (c.155A>C) pathogenic?

ARMC2 p.Gln52Pro (c.155A>C) is classified Likely benign in ARMC2 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-12-01). AlphaMissense: likely benign (0.1242); Rare (popmax 0.198%, nfe).

How common is ARMC2 p.Gln52Pro (c.155A>C) in the general population?

ARMC2 p.Gln52Pro (c.155A>C) is rare (popmax 0.198%, nfe) (gnomAD).

What do computational predictors say about ARMC2 p.Gln52Pro (c.155A>C)?

AlphaMissense predicts likely benign (score 0.1242) — an in-silico prediction, not a clinical call.

ARMC2 p.Gln52Pro

c.155A>C · rs147935937 · VCV3050582

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1242 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.198%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1242	likely benign
REVEL	0.32	indeterminate
SaProt	LLR -6.38	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 1.4, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 119 kb · p 0.00055 · regional, not allelic
Overall
CADD	22.1	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 0.198% European (non-Finnish) · 2,332/1,179,828 alleles

Filtering AF 0.191% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.188%

Overall 0.199% 3,211/1,613,620 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	2.26%	44
Remaining individualsnot grpmax-eligible	0.256%	391
European (non-Finnish)grpmax	0.198%	506
Finnishnot grpmax-eligible	0.0297%	3,366
African / African-American	0.0267%	3,746
Admixed American	0.0167%	6,000
Middle Eastern	0.0165%	6,060
East Asian	0.00223%	44,802

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ARMC2
Protein: p.Gln52Pro
Coding: c.155A>C
MANE Select: NM_032131
dbSNP: rs147935937
Type: single nucleotide variant
Location: chr6:108854422 (GRCh38)
Gene constraint: LOEUF 0.936 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.57
Residue 52: the 'disordered' region

Full ARMC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARMC2 c.2153-1G>C Likely pathogenic ★ same type
ARMC2 p.Asn743Asp Likely pathogenic ★ same type
ARMC2 p.Ala123Val Uncertain significance ★ ⚠ same type
ARMC2 p.Ala143Thr Uncertain significance ★ ⚠ same type
ARMC2 p.Ala231Thr Uncertain significance ★ ⚠ same type
ARMC2 p.Ala260Pro Uncertain significance ★ ⚠ same type
ARMC2 p.Ala292Asp Uncertain significance ★ ⚠ same type
ARMC2 p.Ala495Val 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/armc2-p-gln52pro (accessed [today's date]).

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