Is WRAP53 p.Arg307Trp (c.919C>T) pathogenic?

WRAP53 p.Arg307Trp (c.919C>T) is classified Uncertain significance in WRAP53 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2024-04-10). AlphaMissense: likely benign (0.2131); Ultra-rare (popmax 0.0883%, amr); Associated with WRAP53-related disorder.

What condition is associated with WRAP53 p.Arg307Trp (c.919C>T)?

WRAP53 p.Arg307Trp (c.919C>T) is associated with WRAP53-related disorder, dyskeratosis congenita, autosomal recessive 3 (ClinVar).

How common is WRAP53 p.Arg307Trp (c.919C>T) in the general population?

WRAP53 p.Arg307Trp (c.919C>T) is ultra-rare (popmax 0.0883%, amr) (gnomAD).

What do computational predictors say about WRAP53 p.Arg307Trp (c.919C>T)?

AlphaMissense predicts likely benign (score 0.2131) — an in-silico prediction, not a clinical call.

WRAP53 p.Arg307Trp

c.919C>T · rs149828392 · VCV1163410

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.2131 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0883%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

WRAP53-related disorder

Computational evidence

Protein change
AlphaMissense	0.2131	likely benign
REVEL	0.498	indeterminate
SaProt	LLR -14.01	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -0.08, phastCons 0.98
Regional constraint	o/e 0.97	unconstrained · MANE · 14 kb · p 0.54 · regional, not allelic
Overall
CADD	25.0	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 0.0883% Admixed American · 53/60,016 alleles

Filtering AF 0.0693% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0625%

Overall 0.052% 839/1,614,116 alleles · ultra-rare exomes 753/1,461,800 · genomes 86/152,316 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.1%	91
Admixed Americangrpmax	0.0883%	1,132
European (non-Finnish)	0.0616%	1,623
Remaining individualsnot grpmax-eligible	0.0352%	2,841
Ashkenazi Jewishnot grpmax-eligible	0.0236%	4,229
African / African-American	0.012%	8,340
South Asian	0.00878%	11,385
Finnishnot grpmax-eligible	0.00469%	21,331

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: WRAP53
Protein: p.Arg307Trp
Coding: c.919C>T
MANE Select: NM_001143992
dbSNP: rs149828392
Type: single nucleotide variant
Location: chr17:7701753 (GRCh38)
Gene constraint: LOEUF 0.645 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 73.96 · 7 PDB
Residue 307: a β-strand

Full WRAP53 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

WRAP53-related disorder

Also linked: dyskeratosis congenita, autosomal recessive 3

Similar variants

WRAP53 p.Arg307Gln Uncertain significance ★★ ⚠ same residue
WRAP53 p.Arg307Pro Uncertain significance ★ ⚠ same residue
WRAP53 p.Arg265Gln Uncertain significance ★★ ⚠ same condition
WRAP53 p.Arg298Gln Uncertain significance ★★ ⚠ same condition
WRAP53 p.Arg298Trp Uncertain significance ★★ same condition
WRAP53 p.Arg483His Uncertain significance ★★ ⚠ same condition
WRAP53 p.Arg506Cys Uncertain significance ★★ ⚠ same condition
WRAP53 p.Arg506His 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/wrap53-p-arg307trp (accessed [today's date]).

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