Is ARMC5 p.Ala310Asp (c.929C>A) pathogenic?

ARMC5 p.Ala310Asp (c.929C>A) is classified Uncertain significance in ARMC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: ambiguous (0.4322); Very rare (popmax 0.000509%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ARMC5 p.Ala310Asp (c.929C>A)?

ARMC5 p.Ala310Asp (c.929C>A) is associated with Inborn genetic diseases (ClinVar).

How common is ARMC5 p.Ala310Asp (c.929C>A) in the general population?

ARMC5 p.Ala310Asp (c.929C>A) is very rare (popmax 0.000509%, nfe) (gnomAD).

What do computational predictors say about ARMC5 p.Ala310Asp (c.929C>A)?

AlphaMissense predicts ambiguous (score 0.4322) — an in-silico prediction, not a clinical call.

ARMC5 p.Ala310Asp

c.929C>A · VCV4146920

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4322 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4322	ambiguous
REVEL	0.201	benign-leaning
SaProt	LLR -8.08	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 4,961 bp · p 1.6e-10 · regional, not allelic
Overall
CADD	22.4	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 0.000509% European (non-Finnish) · 6/1,179,790 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,612,288 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.Ala310Asp
Coding: c.929C>A
MANE Select: NM_001105247
Type: single nucleotide variant
Location: chr16:31462476 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.27
Residue 310: 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.Ala310Thr Uncertain significance ★ ⚠ same residue
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

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-ala310asp (accessed [today's date]).

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