Is ATL3 p.Lys71Arg (c.212A>G) pathogenic?

ATL3 p.Lys71Arg (c.212A>G) is classified Uncertain significance in ATL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-04). AlphaMissense: likely benign (0.3328); Very rare (popmax 0.00186%, nfe); Associated with neuropathy, hereditary sensory, type 1F.

What condition is associated with ATL3 p.Lys71Arg (c.212A>G)?

ATL3 p.Lys71Arg (c.212A>G) is associated with neuropathy, hereditary sensory, type 1F (ClinVar).

How common is ATL3 p.Lys71Arg (c.212A>G) in the general population?

ATL3 p.Lys71Arg (c.212A>G) is very rare (popmax 0.00186%, nfe) (gnomAD).

What do computational predictors say about ATL3 p.Lys71Arg (c.212A>G)?

AlphaMissense predicts likely benign (score 0.3328) — an in-silico prediction, not a clinical call.

ATL3 p.Lys71Arg

Q: How is Hereditary sensory and autonomic neuropathy type 1 inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.212A>G · rs2134523954 · VCV1425315

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3328 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00186%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

neuropathy, hereditary sensory, type 1F

Computational evidence

Protein change
AlphaMissense	0.3328	likely benign
REVEL	0.335	indeterminate
SaProt	LLR -11.59	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 42 kb · p 0.12 · regional, not allelic
Overall
CADD	25.9	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 0.00186% European (non-Finnish) · 22/1,180,032 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.0015% 22/1,461,888 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: ATL3
Protein: p.Lys71Arg
Coding: c.212A>G
MANE Select: NM_015459
dbSNP: rs2134523954
Type: single nucleotide variant
Location: chr11:63659087 (GRCh38)
Gene constraint: LOEUF 0.891 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.30 · 2 PDB
Residue 71: a binding site; the gb1/rhd3-type g domain

Full ATL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neuropathy, hereditary sensory, type 1F — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary sensory and autonomic neuropathy type 1 (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages

Similar variants

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ATL3 c.711+1G>T Uncertain significance ★★ same condition
ATL3 c.850+5G>A Uncertain significance ★★ same condition
ATL3 p.Ala457Val Uncertain significance ★★ ⚠ same condition
ATL3 p.Ala508Thr Uncertain significance ★★ ⚠ same condition
ATL3 p.Ala540Ser Uncertain significance ★★ ⚠ 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/atl3-p-lys71arg (accessed [today's date]).

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