Is ATRN p.Thr156= (c.468G>A) pathogenic?

ATRN p.Thr156= (c.468G>A) is classified Likely benign in ATRN (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-01). Ultra-rare (popmax 0.017%, mid); Associated with ATRN-related disorder.

What condition is associated with ATRN p.Thr156= (c.468G>A)?

ATRN p.Thr156= (c.468G>A) is associated with ATRN-related disorder (ClinVar).

How common is ATRN p.Thr156= (c.468G>A) in the general population?

ATRN p.Thr156= (c.468G>A) is ultra-rare (popmax 0.017%, mid) (gnomAD).

ATRN p.Thr156=

c.468G>A · rs375750291 · VCV3035309

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.017%, mid)

Conditions

ATRN-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4
Overall
CADD	4.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.017% Middle Eastern · 1/5,882 alleles

Filtering AF 0.00223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00197%

Overall 0.00278% 43/1,549,340 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.017%	5,882
Remaining individualsnot grpmax-eligible	0.00844%	11,849
European (non-Finnish)	0.00307%	32,579
African / African-American	0.00138%	72,648
South Asian	0.00121%	82,352

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.Thr156=
Coding: c.468G>A
MANE Select: NM_139321
dbSNP: rs375750291
Type: single nucleotide variant
Location: chr20:3535310 (GRCh38)
Gene constraint: LOEUF 0.395 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.27
Residue 156: the cub domain

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.Asp412His 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

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-thr156 (accessed [today's date]).

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