Is ARMC5 p.Pro157Ser (c.469C>T) pathogenic?

ARMC5 p.Pro157Ser (c.469C>T) is classified Uncertain significance in ARMC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-02). AlphaMissense: likely benign (0.1203); Very rare (popmax 0.000424%, nfe); Associated with ARMC5-related disorder.

What condition is associated with ARMC5 p.Pro157Ser (c.469C>T)?

ARMC5 p.Pro157Ser (c.469C>T) is associated with ARMC5-related disorder (ClinVar).

How common is ARMC5 p.Pro157Ser (c.469C>T) in the general population?

ARMC5 p.Pro157Ser (c.469C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about ARMC5 p.Pro157Ser (c.469C>T)?

AlphaMissense predicts likely benign (score 0.1203) — an in-silico prediction, not a clinical call.

ARMC5 p.Pro157Ser

c.469C>T · rs267604526 · VCV2631770

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1203 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ARMC5-related disorder

Computational evidence

Protein change
AlphaMissense	0.1203	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -12.65	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.5	GERP -4.5
Regional constraint	o/e 1.40	unconstrained · MANE · 2,399 bp · p 1.1e-09 · regional, not allelic
Overall
CADD	5.531	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 0.000424% European (non-Finnish) · 5/1,178,298 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000346% 5/1,444,424 alleles · very rare

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: ARMC5
Protein: p.Pro157Ser
Coding: c.469C>T
MANE Select: NM_001105247
dbSNP: rs267604526
Type: single nucleotide variant
Location: chr16:31459993 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.27
Residue 157: a UniProt-annotated variant site (in aimah2; uncertain significance); a UniProt-annotated variant site (in aimah2)

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

Disease context

ARMC5-related disorder

Similar variants

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.Arg315Pro Likely 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-pro157ser (accessed [today's date]).

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