Is DLEU7 p.Arg77Pro (c.230G>C) pathogenic?

DLEU7 p.Arg77Pro (c.230G>C) is classified Uncertain significance in DLEU7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-09). AlphaMissense: likely benign (0.0892); Very rare (popmax 0.0027%, nfe).

How common is DLEU7 p.Arg77Pro (c.230G>C) in the general population?

DLEU7 p.Arg77Pro (c.230G>C) is very rare (popmax 0.0027%, nfe) (gnomAD).

What do computational predictors say about DLEU7 p.Arg77Pro (c.230G>C)?

AlphaMissense predicts likely benign (score 0.0892) — an in-silico prediction, not a clinical call.

DLEU7 p.Arg77Pro

c.230G>C · VCV3502309

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0892 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0027%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0892	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -6.88	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 -0.98	GERP -6.2
Regional constraint	o/e 0.98	unconstrained · MANE · 20 kb · p 0.7 · regional, not allelic
Overall
CADD	3.231	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0027% European (non-Finnish) · 28/1,037,892 alleles

Filtering AF 0.00187% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.00213% 28/1,317,254 alleles · very rare

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: DLEU7
Protein: p.Arg77Pro
Coding: c.230G>C
MANE Select: NM_001306135
Type: single nucleotide variant
Location: chr13:50843417 (GRCh38)
Gene constraint: LOEUF 1.902 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.45
Residue 77: the 'disordered' region

Full DLEU7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLEU7 p.Ala2Val Uncertain significance ★ ⚠ same type
DLEU7 p.Ala49Thr Uncertain significance ★ ⚠ same type
DLEU7 p.Ala51Thr Uncertain significance ★ ⚠ same type
DLEU7 p.Ala80Thr Uncertain significance ★ ⚠ same type
DLEU7 p.Ala83Pro Uncertain significance ★ ⚠ same type
DLEU7 p.Ala9Ser Uncertain significance ★ ⚠ same type
DLEU7 p.Arg123Gly Uncertain significance ★ ⚠ same type
DLEU7 p.Arg52Ser 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/dleu7-p-arg77pro (accessed [today's date]).

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