Is ARC p.Asp307Glu (c.921C>G) pathogenic?

ARC p.Asp307Glu (c.921C>G) is classified Uncertain significance in ARC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-03). AlphaMissense: likely pathogenic (0.7557); Absent from gnomAD v4.1.

How common is ARC p.Asp307Glu (c.921C>G) in the general population?

ARC p.Asp307Glu (c.921C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARC p.Asp307Glu (c.921C>G)?

AlphaMissense predicts likely pathogenic (score 0.7557) — an in-silico prediction, not a clinical call.

ARC p.Asp307Glu

c.921C>G · rs2539792963 · VCV2293937

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7557 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7557	likely pathogenic
REVEL	0.149	moderately benign-leaning
SaProt	LLR -6.22	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 0.42, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 449 bp · p 2.8e-08 · regional, not allelic
Overall
CADD	21.4	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

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: ARC
Protein: p.Asp307Glu
Coding: c.921C>G
MANE Select: NM_015193
dbSNP: rs2539792963
Type: single nucleotide variant
Location: chr8:142613351 (GRCh38)
Gene constraint: LOEUF 1.393 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.72 · 11 PDB
Residue 307: an α-helix

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

Similar variants

ARC c.*258C>T Benign ★★ same type
ARC p.Ala144Ser Uncertain significance ★ ⚠ same type
ARC p.Arg107Cys Uncertain significance ★ ⚠ same type
ARC p.Arg129His Uncertain significance ★ ⚠ same type
ARC p.Arg304His Uncertain significance ★ ⚠ same type
ARC p.Arg335Cys Uncertain significance ★ ⚠ same type
ARC p.Arg392Gln Uncertain significance ★ ⚠ same type
ARC p.Asp374Asn 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/arc-p-asp307glu (accessed [today's date]).

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