Is ATRN p.Ser263Arg (c.787A>C) pathogenic?

ATRN p.Ser263Arg (c.787A>C) is classified Uncertain significance in ATRN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-18). AlphaMissense: likely benign (0.117); Ultra-rare (popmax 0.0209%, sas).

How common is ATRN p.Ser263Arg (c.787A>C) in the general population?

ATRN p.Ser263Arg (c.787A>C) is ultra-rare (popmax 0.0209%, sas) (gnomAD).

What do computational predictors say about ATRN p.Ser263Arg (c.787A>C)?

AlphaMissense predicts likely benign (score 0.117) — an in-silico prediction, not a clinical call.

ATRN p.Ser263Arg

c.787A>C · rs748613292 · VCV3132149

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.117 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0209%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.117	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -7.00	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 3.5	phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 106 kb · p 0.00041 · regional, not allelic
Overall
CADD	19.67	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 0.0209% South Asian · 19/91,088 alleles

Filtering AF 0.0136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0114%

Overall 0.00118% 19/1,614,180 alleles · ultra-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.Ser263Arg
Coding: c.787A>C
MANE Select: NM_139321
dbSNP: rs748613292
Type: single nucleotide variant
Location: chr20:3547333 (GRCh38)
Gene constraint: LOEUF 0.395 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.27
Residue 263: a disulfide bond

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-ser263arg (accessed [today's date]).

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