Is ARMC5 p.Arg315Pro (c.944G>C) pathogenic?

ARMC5 p.Arg315Pro (c.944G>C) is classified Likely pathogenic in ARMC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-02). AlphaMissense: likely pathogenic (0.968); Absent from gnomAD v4.1; Associated with ARMC5-related disorder.

What condition is associated with ARMC5 p.Arg315Pro (c.944G>C)?

ARMC5 p.Arg315Pro (c.944G>C) is associated with ARMC5-related disorder (ClinVar).

How common is ARMC5 p.Arg315Pro (c.944G>C) in the general population?

ARMC5 p.Arg315Pro (c.944G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARMC5 p.Arg315Pro (c.944G>C)?

AlphaMissense predicts likely pathogenic (score 0.968) — an in-silico prediction, not a clinical call.

ARMC5 p.Arg315Pro

c.944G>C · VCV4929623

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.968 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ARMC5-related disorder

Computational evidence

Protein change
AlphaMissense	0.968	likely pathogenic ✓ concordant with ClinVar · top 5% in ARMC5
REVEL	0.558	indeterminate
SaProt	LLR -13.80	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 4,961 bp · p 1.6e-10 · regional, not allelic
Overall
CADD	25.7	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: ARMC5
Protein: p.Arg315Pro
Coding: c.944G>C
MANE Select: NM_001105247
Type: single nucleotide variant
Location: chr16:31462491 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.27
Residue 315: a UniProt-annotated variant site (in aimah2; uncertain significance); a UniProt-annotated variant site (in aimah2); a UniProt-annotated variant site (in aimah2; loss of function in promoting apoptosis; decreased association with polr2a component of rna polymerase ii; reduced ability to promote degradation of srebf1)

Full ARMC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ARMC5-related disorder

Similar variants

ARMC5 p.Arg315Trp Likely pathogenic ★ same residue
ARMC5 p.Arg173Ter Pathogenic ★★ same condition
ARMC5 p.Arg690Gln Uncertain significance ★★ ⚠ same condition
ARMC5 p.Pro606Leu Uncertain significance ★★ ⚠ same condition
ARMC5 p.Arg267Ter Pathogenic ★ same condition
ARMC5 p.Gln759Ter Likely pathogenic ★ same condition
ARMC5 p.Ser107Ter Likely pathogenic ★ same condition
ARMC5 c.1864+168C>T Uncertain significance ★ same condition

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/armc5-p-arg315pro (accessed [today's date]).

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