Is DERA p.Leu71Val (c.211C>G) pathogenic?

DERA p.Leu71Val (c.211C>G) is classified Uncertain significance in DERA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-04). AlphaMissense: likely benign (0.2867); Very rare (popmax 0.00478%, nfe).

How common is DERA p.Leu71Val (c.211C>G) in the general population?

DERA p.Leu71Val (c.211C>G) is very rare (popmax 0.00478%, nfe) (gnomAD).

What do computational predictors say about DERA p.Leu71Val (c.211C>G)?

AlphaMissense predicts likely benign (score 0.2867) — an in-silico prediction, not a clinical call.

DERA p.Leu71Val

c.211C>G · VCV4010997

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2867 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00478%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2867	likely benign
REVEL	0.397	indeterminate
SaProt	LLR -12.40	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 125 kb · p 0.71 · regional, not allelic
Overall
CADD	26.4	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 0.00478% European (non-Finnish) · 56/1,172,426 alleles

Filtering AF 0.00377% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00339%

Overall 0.00356% 57/1,599,620 alleles · very rare exomes 57/1,447,324 · genomes 0/152,296 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00478%	20,936
Remaining individualsnot grpmax-eligible	0.00161%	61,980

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.Leu71Val
Coding: c.211C>G
MANE Select: NM_015954
Type: single nucleotide variant
Location: chr12:15958269 (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.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
DERA p.Arg176Cys 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-leu71val (accessed [today's date]).

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