Is ARMC6 p.Phe117Leu (c.351C>G) pathogenic?

ARMC6 p.Phe117Leu (c.351C>G) is classified Uncertain significance in ARMC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). AlphaMissense: likely pathogenic (0.7951); Absent from gnomAD v4.1.

How common is ARMC6 p.Phe117Leu (c.351C>G) in the general population?

ARMC6 p.Phe117Leu (c.351C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARMC6 p.Phe117Leu (c.351C>G)?

AlphaMissense predicts likely pathogenic (score 0.7951) — an in-silico prediction, not a clinical call.

ARMC6 p.Phe117Leu

c.351C>G · rs2514036848 · VCV3129667

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7951 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7951	likely pathogenic · top 9% in ARMC6
REVEL	0.15	moderately benign-leaning
SaProt	LLR 0.69	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.41	GERP -3, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 23 kb · p 0.035 · regional, not allelic
Overall
CADD	7.723	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARMC6
Protein: p.Phe117Leu
Coding: c.351C>G
MANE Select: NM_001199196
dbSNP: rs2514036848
Type: single nucleotide variant
Location: chr19:19051693 (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-phe117leu (accessed [today's date]).

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