Is ARMC8 p.Glu296Gln (c.886G>C) pathogenic?

ARMC8 p.Glu296Gln (c.886G>C) is classified Uncertain significance in ARMC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-06). AlphaMissense: ambiguous (0.5113); Very rare (popmax 0.005%, amr).

How common is ARMC8 p.Glu296Gln (c.886G>C) in the general population?

ARMC8 p.Glu296Gln (c.886G>C) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about ARMC8 p.Glu296Gln (c.886G>C)?

AlphaMissense predicts ambiguous (score 0.5113) — an in-silico prediction, not a clinical call.

ARMC8 p.Glu296Gln

c.886G>C · rs143059438 · VCV2343683

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5113 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Computational evidence

Protein change
AlphaMissense	0.5113	ambiguous
REVEL	0.313	indeterminate
SaProt	LLR -8.04	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 54 kb · p 0.012 · regional, not allelic
Overall
CADD	23.9	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 0.005% Admixed American · 3/59,996 alleles

Filtering AF 0.00315% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00279%

Overall 0.0201% 325/1,613,916 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.787%	127
Remaining individualsnot grpmax-eligible	0.0656%	1,524
Admixed Americangrpmax	0.005%	19,999
European (non-Finnish)	0.00407%	24,583

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: ARMC8
Protein: p.Glu296Gln
Coding: c.886G>C
MANE Select: NM_001363941
dbSNP: rs143059438
Type: single nucleotide variant
Location: chr3:138241831 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 94.16 · 1 PDB
Residue 296: an α-helix

Full ARMC8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARMC8 p.Ala403Thr Uncertain significance ★ ⚠ same type
ARMC8 p.Ala469Thr Uncertain significance ★ ⚠ same type
ARMC8 p.Arg159Lys Uncertain significance ★ ⚠ same type
ARMC8 p.Arg161His Uncertain significance ★ ⚠ same type
ARMC8 p.Arg270Gln Uncertain significance ★ ⚠ same type
ARMC8 p.Arg270Trp Uncertain significance ★ ⚠ same type
ARMC8 p.Arg376Trp Uncertain significance ★ ⚠ same type
ARMC8 p.Arg542Cys 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/armc8-p-glu296gln (accessed [today's date]).

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