Is ATRN p.Lys1124Arg (c.3371A>G) pathogenic?

ATRN p.Lys1124Arg (c.3371A>G) is classified Uncertain significance in ATRN (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-15). AlphaMissense: likely benign (0.0898); Very rare (popmax 0.00017%, nfe).

How common is ATRN p.Lys1124Arg (c.3371A>G) in the general population?

ATRN p.Lys1124Arg (c.3371A>G) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about ATRN p.Lys1124Arg (c.3371A>G)?

AlphaMissense predicts likely benign (score 0.0898) — an in-silico prediction, not a clinical call.

ATRN p.Lys1124Arg

c.3371A>G · rs771215598 · VCV2261705

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0898 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0898	likely benign
REVEL	0.206	benign-leaning
SaProt	LLR -7.09	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 2, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 56 kb · p 4.8e-13 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,178,996 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,460,396 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.Lys1124Arg
Coding: c.3371A>G
MANE Select: NM_139321
dbSNP: rs771215598
Type: single nucleotide variant
Location: chr20:3594527 (GRCh38)
Gene constraint: LOEUF 0.395 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.27
Residue 1124: the laminin egf-like 2 domain

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-lys1124arg (accessed [today's date]).

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