Is ATRN p.Asp412His (c.1234G>C) pathogenic?

ATRN p.Asp412His (c.1234G>C) is classified Uncertain significance in ATRN (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-06-15). AlphaMissense: likely pathogenic (0.8856); Absent from gnomAD v4.1; Associated with ATRN-related disorder.

What condition is associated with ATRN p.Asp412His (c.1234G>C)?

ATRN p.Asp412His (c.1234G>C) is associated with ATRN-related disorder (ClinVar).

How common is ATRN p.Asp412His (c.1234G>C) in the general population?

ATRN p.Asp412His (c.1234G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ATRN p.Asp412His (c.1234G>C)?

AlphaMissense predicts likely pathogenic (score 0.8856) — an in-silico prediction, not a clinical call.

ATRN p.Asp412His

c.1234G>C · VCV3347044

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8856 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ATRN-related disorder

Computational evidence

Protein change
AlphaMissense	0.8856	likely pathogenic
REVEL	0.661	pathogenic-leaning
SaProt	LLR -4.23	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 106 kb · p 0.00041 · regional, not allelic
Overall
CADD	27.0	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: ATRN
Protein: p.Asp412His
Coding: c.1234G>C
MANE Select: NM_139321
Type: single nucleotide variant
Location: chr20:3560692 (GRCh38)
Gene constraint: LOEUF 0.395 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.27

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

Disease context

ATRN-related disorder

Similar variants

ATRN p.Cys318Arg Uncertain significance ★★ ⚠ same condition
ATRN p.Gly164Val Uncertain significance ★★ ⚠ same condition
ATRN p.Glu127Ter Uncertain significance ★ same condition
ATRN p.Asn1206Ser Uncertain significance ⚠ same condition
ATRN p.Leu454Arg Uncertain significance ⚠ same condition
ATRN c.1203+8A>G Likely benign same condition
ATRN c.-44T>G Likely benign same condition
ATRN p.Gly134= Likely benign 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/atrn-p-asp412his (accessed [today's date]).

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