Is DERA p.Arg105Trp (c.313C>T) pathogenic?

DERA p.Arg105Trp (c.313C>T) is classified Uncertain significance in DERA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). AlphaMissense: likely benign (0.3179); Very rare (popmax 0.00238%, sas).

How common is DERA p.Arg105Trp (c.313C>T) in the general population?

DERA p.Arg105Trp (c.313C>T) is very rare (popmax 0.00238%, sas) (gnomAD).

What do computational predictors say about DERA p.Arg105Trp (c.313C>T)?

AlphaMissense predicts likely benign (score 0.3179) — an in-silico prediction, not a clinical call.

DERA p.Arg105Trp

c.313C>T · rs375747326 · VCV3081776

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3179 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00238%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3179	likely benign
REVEL	0.305	indeterminate
SaProt	LLR -16.77	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.57 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.7	GERP 1.7, phastCons 0.99
Regional constraint	o/e 0.98	unconstrained · MANE · 125 kb · p 0.71 · regional, not allelic
Overall
CADD	26.3	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 0.00238% South Asian · 2/83,956 alleles

Filtering AF 0.00158% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00193% 30/1,550,672 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00238%	41,978
European (non-Finnish)	0.00227%	44,057
Admixed American	0.00195%	51,340
African / African-American	0.00137%	73,096

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.Arg105Trp
Coding: c.313C>T
MANE Select: NM_015954
dbSNP: rs375747326
Type: single nucleotide variant
Location: chr12:15959864 (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.Arg105Gly 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.Arg176Cys Uncertain significance ★ ⚠ same type
DERA p.Arg179Cys 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-arg105trp (accessed [today's date]).

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