Is ARMC6 p.Arg366His (c.1097G>A) pathogenic?

ARMC6 p.Arg366His (c.1097G>A) is classified Likely benign in ARMC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-13). AlphaMissense: likely benign (0.0709); Rare (popmax 0.512%, mid).

How common is ARMC6 p.Arg366His (c.1097G>A) in the general population?

ARMC6 p.Arg366His (c.1097G>A) is rare (popmax 0.512%, mid) (gnomAD).

What do computational predictors say about ARMC6 p.Arg366His (c.1097G>A)?

AlphaMissense predicts likely benign (score 0.0709) — an in-silico prediction, not a clinical call.

ARMC6 p.Arg366His

c.1097G>A · rs374945143 · VCV2534802

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0709 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.512%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0709	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -7.12	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 -0.67	GERP -2.9
Regional constraint	o/e 0.92	unconstrained · MANE · 23 kb · p 0.035 · regional, not allelic
Overall
CADD	2.509	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 0.512% Middle Eastern · 31/6,058 alleles

Filtering AF 0.37% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.322%

Overall 0.0143% 231/1,613,446 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.512%	195
South Asian	0.0857%	1,167
Remaining individualsnot grpmax-eligible	0.0464%	2,154
European (non-Finnish)	0.00721%	13,878
East Asian	0.00669%	14,941
Admixed American	0.00501%	19,977
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,572
African / African-American	0.00133%	75,028

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: ARMC6
Protein: p.Arg366His
Coding: c.1097G>A
MANE Select: NM_001199196
dbSNP: rs374945143
Type: single nucleotide variant
Location: chr19:19055338 (GRCh38)
Gene constraint: LOEUF 1.112 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.10

Full ARMC6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARMC6 p.Ala131Thr Uncertain significance ★ ⚠ same type
ARMC6 p.Ala131Val Uncertain significance ★ ⚠ same type
ARMC6 p.Ala132Val Uncertain significance ★ ⚠ same type
ARMC6 p.Ala161Val Uncertain significance ★ ⚠ same type
ARMC6 p.Ala32Gly Uncertain significance ★ ⚠ same type
ARMC6 p.Ala355Thr Uncertain significance ★ ⚠ same type
ARMC6 p.Ala392Thr Uncertain significance ★ ⚠ same type
ARMC6 p.Ala447Val 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/armc6-p-arg366his (accessed [today's date]).

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