Is ATRN p.Leu68= (c.204C>G) pathogenic?

ATRN p.Leu68= (c.204C>G) is classified Likely benign in ATRN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-06). Very rare (popmax 0.00288%, eas).

How common is ATRN p.Leu68= (c.204C>G) in the general population?

ATRN p.Leu68= (c.204C>G) is very rare (popmax 0.00288%, eas) (gnomAD).

ATRN p.Leu68=

c.204C>G · rs1363808562 · VCV1934192

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00288%, eas)

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 -0.87	GERP -0.12
Overall
CADD	7.516	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00288% East Asian · 1/34,724 alleles

Overall 0.000135% 2/1,481,962 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00288%	34,724
European (non-Finnish)	8.89e-05%	1,125,444

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.Leu68=
Coding: c.204C>G
MANE Select: NM_139321
dbSNP: rs1363808562
Type: single nucleotide variant
Location: chr20:3471311 (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.Leu68Pro Uncertain significance ★ ⚠ same residue
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

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-leu68 (accessed [today's date]).

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