Is ARMC5 p.Ala80Val (c.239C>T) pathogenic?

ARMC5 p.Ala80Val (c.239C>T) is classified Uncertain significance in ARMC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-07). AlphaMissense: likely benign (0.1118); Very rare (popmax 0.0025%, eas); Associated with Inborn genetic diseases.

What condition is associated with ARMC5 p.Ala80Val (c.239C>T)?

ARMC5 p.Ala80Val (c.239C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ARMC5 p.Ala80Val (c.239C>T) in the general population?

ARMC5 p.Ala80Val (c.239C>T) is very rare (popmax 0.0025%, eas) (gnomAD).

What do computational predictors say about ARMC5 p.Ala80Val (c.239C>T)?

AlphaMissense predicts likely benign (score 0.1118) — an in-silico prediction, not a clinical call.

ARMC5 p.Ala80Val

c.239C>T · rs1197883705 · VCV2481535

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1118 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0025%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1118	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -7.29	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 2.1	GERP 2.1, phastCons 1
Regional constraint	o/e 1.40	unconstrained · MANE · 2,399 bp · p 1.1e-09 · regional, not allelic
Overall
CADD	19.64	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0025% East Asian · 1/40,060 alleles

Overall 0.000195% 3/1,534,796 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0025%	40,060
Remaining individualsnot grpmax-eligible	0.00168%	59,602
European (non-Finnish)	8.7e-05%	1,149,338

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.Ala80Val
Coding: c.239C>T
MANE Select: NM_001105247
dbSNP: rs1197883705
Type: single nucleotide variant
Location: chr16:31459763 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.27
Residue 80: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARMC5 p.Ala55Val Uncertain significance ★★ ⚠ same condition
ARMC5 p.Arg611Leu Uncertain significance ★★ ⚠ same condition
ARMC5 p.Ser266Thr Uncertain significance ★★ ⚠ same condition
ARMC5 p.Trp801Cys Uncertain significance ★★ ⚠ same condition
ARMC5 p.Ala100Thr Uncertain significance ★ ⚠ same condition
ARMC5 p.Ala206Ser Uncertain significance ★ ⚠ same condition
ARMC5 p.Ala22Val Uncertain significance ★ ⚠ same condition
ARMC5 p.Ala243Gly 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-ala80val (accessed [today's date]).

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