Is DERA p.Trp42Arg (c.124T>A) pathogenic?

DERA p.Trp42Arg (c.124T>A) is classified Uncertain significance in DERA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-04). AlphaMissense: likely pathogenic (0.8634); Very rare (popmax 0.00501%, amr).

How common is DERA p.Trp42Arg (c.124T>A) in the general population?

DERA p.Trp42Arg (c.124T>A) is very rare (popmax 0.00501%, amr) (gnomAD).

What do computational predictors say about DERA p.Trp42Arg (c.124T>A)?

AlphaMissense predicts likely pathogenic (score 0.8634) — an in-silico prediction, not a clinical call.

DERA p.Trp42Arg

c.124T>A · rs761047506 · VCV3081773

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8634 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00501%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8634	likely pathogenic
REVEL	0.443	indeterminate
SaProt	LLR -7.95	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 125 kb · p 0.71 · regional, not allelic
Overall
CADD	27.8	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 0.00501% Admixed American · 3/59,934 alleles

Filtering AF 0.00223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00198%

Overall 0.0026% 42/1,612,996 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00501%	19,978
South Asian	0.0033%	30,345
European (non-Finnish)	0.00305%	32,762

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: DERA
Protein: p.Trp42Arg
Coding: c.124T>A
MANE Select: NM_015954
dbSNP: rs761047506
Type: single nucleotide variant
Location: chr12:15957028 (GRCh38)
Gene constraint: LOEUF 0.658 · pLI 0.34 (gnomAD)
Structure: AlphaFold pLDDT 95.99

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

Similar variants

DERA p.Trp42Cys Uncertain significance ★ ⚠ same residue
DERA p.Ala115Ser Uncertain significance ★ ⚠ same type
DERA p.Ala131Thr Uncertain significance ★ ⚠ same type
DERA p.Ala228Gly Uncertain significance ★ ⚠ same type
DERA p.Ala262Val Uncertain significance ★ ⚠ same type
DERA p.Ala29Val Uncertain significance ★ ⚠ same type
DERA p.Arg105Gly Uncertain significance ★ ⚠ same type
DERA p.Arg105Trp 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/dera-p-trp42arg (accessed [today's date]).

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