Is ARCN1 p.Val147Ala (c.440T>C) pathogenic?

ARCN1 p.Val147Ala (c.440T>C) is classified Uncertain significance in ARCN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-02). AlphaMissense: likely pathogenic (0.9948); Absent from gnomAD v4.1; Associated with short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay.

How common is ARCN1 p.Val147Ala (c.440T>C) in the general population?

ARCN1 p.Val147Ala (c.440T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARCN1 p.Val147Ala (c.440T>C)?

AlphaMissense predicts likely pathogenic (score 0.9948) — an in-silico prediction, not a clinical call.

ARCN1 p.Val147Ala

Q: What condition is associated with ARCN1 p.Val147Ala (c.440T>C)?

ARCN1 p.Val147Ala (c.440T>C) is associated with short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay (ClinVar).

c.440T>C · rs2497682575 · VCV1805111

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9948 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay

Computational evidence

Protein change
AlphaMissense	0.9948	likely pathogenic
REVEL	0.184	benign-leaning
SaProt	LLR -11.33	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.6, phastCons 1
Regional constraint	o/e 0.56	unconstrained · MANE · 11 kb · p 2.6e-09 · regional, not allelic
Overall
CADD	25.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARCN1
Protein: p.Val147Ala
Coding: c.440T>C
MANE Select: NM_001655
dbSNP: rs2497682575
Type: single nucleotide variant
Location: chr11:118583351 (GRCh38)
Gene constraint: LOEUF 0.145 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 84.25

Full ARCN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARCN1 p.Val147Ile Uncertain significance ★ ⚠ same residue
ARCN1 p.Val147= Likely benign ★ same residue
ARCN1 c.654-15A>G Pathogenic/Likely pathogenic ★★ same condition
ARCN1 p.Arg170Ter Pathogenic ★★ same condition
ARCN1 p.Arg312Ter Pathogenic ★★ same condition
ARCN1 p.Arg314His Uncertain significance ★★ ⚠ same condition
ARCN1 p.Asp426Asn Uncertain significance ★★ ⚠ same condition
ARCN1 p.Ile269Val 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-val147ala (accessed [today's date]).

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