Is ARMS2 p.Pro78Ala (c.232C>G) pathogenic?

ARMS2 p.Pro78Ala (c.232C>G) is classified Uncertain significance in ARMS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-06). AlphaMissense: likely benign (0.1821); Very rare (popmax 0.000763%, nfe).

How common is ARMS2 p.Pro78Ala (c.232C>G) in the general population?

ARMS2 p.Pro78Ala (c.232C>G) is very rare (popmax 0.000763%, nfe) (gnomAD).

What do computational predictors say about ARMS2 p.Pro78Ala (c.232C>G)?

AlphaMissense predicts likely benign (score 0.1821) — an in-silico prediction, not a clinical call.

ARMS2 p.Pro78Ala

c.232C>G · rs1466439612 · VCV2517498

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1821 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1821	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -7.49	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 -4.2	GERP -0.11
Regional constraint	o/e 0.78	unconstrained · MANE · 2,202 bp · p 0.011 · regional, not allelic
Overall
CADD	12.3	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 0.000763% European (non-Finnish) · 9/1,179,816 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000558% 9/1,613,738 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: ARMS2
Protein: p.Pro78Ala
Coding: c.232C>G
MANE Select: NM_001099667
dbSNP: rs1466439612
Type: single nucleotide variant
Location: chr10:122454959 (GRCh38)
Gene constraint: LOEUF 1.815 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 58.14

Full ARMS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARMS2 c.298-13A>G Benign/Likely benign ★★ same type
ARMS2 c.298-13A>T Benign/Likely benign ★★ same type
ARMS2 c.*107T>G Likely benign ★★ same type
ARMS2 c.*373T>G Benign/Likely benign ★★ same type
ARMS2 c.*45T>G Likely benign ★★ same type
ARMS2 p.Ala69Ser Benign ★★ same type
ARMS2 p.Arg38Ter Benign ★★ same type
ARMS2 c.*251T>C 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/arms2-p-pro78ala (accessed [today's date]).

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