Is DENR p.Pro17Ser (c.49C>T) pathogenic?

DENR p.Pro17Ser (c.49C>T) is classified Likely benign in DENR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-16). AlphaMissense: likely benign (0.0574); Very rare (popmax 0.00381%, nfe).

How common is DENR p.Pro17Ser (c.49C>T) in the general population?

DENR p.Pro17Ser (c.49C>T) is very rare (popmax 0.00381%, nfe) (gnomAD).

What do computational predictors say about DENR p.Pro17Ser (c.49C>T)?

AlphaMissense predicts likely benign (score 0.0574) — an in-silico prediction, not a clinical call.

DENR p.Pro17Ser

c.49C>T · rs757045169 · VCV2211353

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0574 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00381%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0574	likely benign
REVEL	0.011	strongly benign-leaning
SaProt	LLR -4.80	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.1	GERP -4
Regional constraint	o/e 0.75	unconstrained · MANE · 14 kb · p 0.0035 · regional, not allelic
Overall
CADD	7.59	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 0.00381% European (non-Finnish) · 45/1,179,892 alleles

Filtering AF 0.00291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0026%

Overall 0.00322% 47/1,461,702 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00381%	26,220
Remaining individualsnot grpmax-eligible	0.0032%	31,243

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: DENR
Protein: p.Pro17Ser
Coding: c.49C>T
MANE Select: NM_003677
dbSNP: rs757045169
Type: single nucleotide variant
Location: chr12:122753750 (GRCh38)
Gene constraint: LOEUF 0.57 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 63.04 · 5 PDB

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

Similar variants

DENR p.Ala21Val Uncertain significance ★ ⚠ same type
DENR p.Asp186Glu Uncertain significance ★ ⚠ same type
DENR p.Asp26Tyr Uncertain significance ★ ⚠ same type
DENR p.Gln96Pro Uncertain significance ★ ⚠ same type
DENR p.Glu77Ala Uncertain significance ★ ⚠ same type
DENR p.Glu89Asp Uncertain significance ★ ⚠ same type
DENR p.Glu89Lys Uncertain significance ★ ⚠ same type
DENR p.Gly194Arg 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/denr-p-pro17ser (accessed [today's date]).

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