Is ARCN1 p.Ser415Cys (c.1244C>G) pathogenic?

ARCN1 p.Ser415Cys (c.1244C>G) is classified Uncertain significance in ARCN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-21). AlphaMissense: likely benign (0.1055); Very rare (popmax 0.00246%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ARCN1 p.Ser415Cys (c.1244C>G)?

ARCN1 p.Ser415Cys (c.1244C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ARCN1 p.Ser415Cys (c.1244C>G) in the general population?

ARCN1 p.Ser415Cys (c.1244C>G) is very rare (popmax 0.00246%, nfe) (gnomAD).

What do computational predictors say about ARCN1 p.Ser415Cys (c.1244C>G)?

AlphaMissense predicts likely benign (score 0.1055) — an in-silico prediction, not a clinical call.

ARCN1 p.Ser415Cys

c.1244C>G · rs782482572 · VCV2284054

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1055 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00246%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1055	likely benign
REVEL	0.188	benign-leaning
SaProt	LLR -10.49	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 5.9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 17 kb · p 0.00011 · regional, not allelic
Overall
CADD	25.5	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 0.00246% European (non-Finnish) · 29/1,179,988 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00186% 30/1,613,836 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00246%	40,689
Remaining individualsnot grpmax-eligible	0.0016%	62,470

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: ARCN1
Protein: p.Ser415Cys
Coding: c.1244C>G
MANE Select: NM_001655
dbSNP: rs782482572
Type: single nucleotide variant
Location: chr11:118597709 (GRCh38)
Gene constraint: LOEUF 0.145 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 84.25
Residue 415: the mhd domain

Full ARCN1 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

ARCN1 p.Arg161His Uncertain significance ★★ ⚠ same condition
ARCN1 p.Asn348His Uncertain significance ★★ ⚠ same condition
ARCN1 p.Asp400Glu Uncertain significance ★★ ⚠ same condition
ARCN1 p.His431Arg Uncertain significance ★★ ⚠ same condition
ARCN1 p.Met276Val Uncertain significance ★★ ⚠ same condition
ARCN1 p.Met302Leu Uncertain significance ★★ ⚠ same condition
ARCN1 p.Pro267Ser Uncertain significance ★★ ⚠ same condition
ARCN1 p.Pro462Ala 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/arcn1-p-ser415cys (accessed [today's date]).

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