Is DRAP1 p.Leu185Phe (c.555G>T) pathogenic?

DRAP1 p.Leu185Phe (c.555G>T) is classified Uncertain significance in DRAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-18). AlphaMissense: likely benign (0.0687); Very rare (popmax 0.00401%, afr).

How common is DRAP1 p.Leu185Phe (c.555G>T) in the general population?

DRAP1 p.Leu185Phe (c.555G>T) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about DRAP1 p.Leu185Phe (c.555G>T)?

AlphaMissense predicts likely benign (score 0.0687) — an in-silico prediction, not a clinical call.

DRAP1 p.Leu185Phe

c.555G>T · VCV3273732

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0687 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0687	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -6.74	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.22	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 3.7	GERP -1, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 1,603 bp · p 0.54 · regional, not allelic
Overall
CADD	19.48	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 0.00401% African / African-American · 3/74,776 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000435% 7/1,610,938 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,925
Remaining individualsnot grpmax-eligible	0.0016%	62,364
South Asian	0.0011%	90,980
European (non-Finnish)	0.00017%	588,786

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: DRAP1
Protein: p.Leu185Phe
Coding: c.555G>T
MANE Select: NM_006442
Type: single nucleotide variant
Location: chr11:65921372 (GRCh38)
Gene constraint: LOEUF 0.738 · pLI 0.18 (gnomAD)
Structure: AlphaFold pLDDT 73.87 · 1 PDB
Residue 185: the 'disordered' region

Full DRAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRAP1 p.Arg109Cys Uncertain significance ★ ⚠ same type
DRAP1 p.Arg112Trp Uncertain significance ★ ⚠ same type
DRAP1 p.Asn100Asp Uncertain significance ★ ⚠ same type
DRAP1 p.Asp105His Uncertain significance ★ ⚠ same type
DRAP1 p.Asp130Glu Uncertain significance ★ ⚠ same type
DRAP1 p.Asp196Asn Uncertain significance ★ ⚠ same type
DRAP1 p.Gln55His Uncertain significance ★ ⚠ same type
DRAP1 p.Glu198Asp 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/drap1-p-leu185phe (accessed [today's date]).

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