Is DERA p.Ala262Val (c.785C>T) pathogenic?

DERA p.Ala262Val (c.785C>T) is classified Uncertain significance in DERA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). AlphaMissense: likely pathogenic (0.6326); Rare (popmax 0.116%, eas).

How common is DERA p.Ala262Val (c.785C>T) in the general population?

DERA p.Ala262Val (c.785C>T) is rare (popmax 0.116%, eas) (gnomAD).

What do computational predictors say about DERA p.Ala262Val (c.785C>T)?

AlphaMissense predicts likely pathogenic (score 0.6326) — an in-silico prediction, not a clinical call.

DERA p.Ala262Val

c.785C>T · rs577064415 · VCV3081778

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6326 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.116%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6326	likely pathogenic
REVEL	0.393	indeterminate
SaProt	LLR -8.58	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.34	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 125 kb · p 0.71 · regional, not allelic
Overall
CADD	33.0	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 0.116% East Asian · 52/44,848 alleles

Filtering AF 0.0907% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0818%

Overall 0.00347% 56/1,613,322 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.116%	862
South Asian	0.0022%	45,493
Remaining individualsnot grpmax-eligible	0.0016%	62,454
European (non-Finnish)	8.48e-05%	1,179,606

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.Ala262Val
Coding: c.785C>T
MANE Select: NM_015954
dbSNP: rs577064415
Type: single nucleotide variant
Location: chr12:16036266 (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.Ala115Ser Uncertain significance ★ ⚠ same type
DERA p.Ala131Thr Uncertain significance ★ ⚠ same type
DERA p.Ala228Gly 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
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-ala262val (accessed [today's date]).

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