Is ATRN p.Ala342Val (c.1025C>T) pathogenic?

ATRN p.Ala342Val (c.1025C>T) is classified Uncertain significance in ATRN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-19). AlphaMissense: likely pathogenic (0.8243); Very rare (popmax 8.49e-05%, nfe).

How common is ATRN p.Ala342Val (c.1025C>T) in the general population?

ATRN p.Ala342Val (c.1025C>T) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about ATRN p.Ala342Val (c.1025C>T)?

AlphaMissense predicts likely pathogenic (score 0.8243) — an in-silico prediction, not a clinical call.

ATRN p.Ala342Val

c.1025C>T · VCV3811252

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8243 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8243	likely pathogenic
REVEL	0.659	pathogenic-leaning
SaProt	LLR -9.64	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 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 106 kb · p 0.00041 · regional, not allelic
Overall
CADD	26.9	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 8.49e-05% European (non-Finnish) · 1/1,178,500 alleles

Overall 6.86e-05% 1/1,458,340 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: ATRN
Protein: p.Ala342Val
Coding: c.1025C>T
MANE Select: NM_139321
Type: single nucleotide variant
Location: chr20:3549251 (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

Similar variants

ATRN p.Ala438Gly Uncertain significance ★★ ⚠ same type
ATRN p.Ala87Val Uncertain significance ★★ ⚠ same type
ATRN p.Arg1417Gln Uncertain significance ★★ ⚠ same type
ATRN p.Arg173His Uncertain significance ★★ ⚠ same type
ATRN p.Asn1035Ser Uncertain significance ★★ ⚠ same type
ATRN p.Asn213Ser Uncertain significance ★★ ⚠ same type
ATRN p.Asn300Thr Uncertain significance ★★ ⚠ same type
ATRN p.Asp508Asn 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/atrn-p-ala342val (accessed [today's date]).

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