Is DLGAP5 p.Arg151Trp (c.451C>T) pathogenic?

DLGAP5 p.Arg151Trp (c.451C>T) is classified Uncertain significance in DLGAP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-14). AlphaMissense: ambiguous (0.4483); Ultra-rare (popmax 0.012%, afr).

How common is DLGAP5 p.Arg151Trp (c.451C>T) in the general population?

DLGAP5 p.Arg151Trp (c.451C>T) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about DLGAP5 p.Arg151Trp (c.451C>T)?

AlphaMissense predicts ambiguous (score 0.4483) — an in-silico prediction, not a clinical call.

DLGAP5 p.Arg151Trp

c.451C>T · VCV3840377

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4483 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4483	ambiguous
REVEL	0.251	benign-leaning
SaProt	LLR -12.36	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.68 · evaluated, not missing
Pangolin	Δ0.23	loss · gain 0.02 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 2.4	GERP -1.2, phastCons 0.72
Regional constraint	o/e 1.05	unconstrained · MANE · 41 kb · p 0.094 · regional, not allelic
Overall
CADD	24.3	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 0.012% African / African-American · 9/74,934 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.00136% 22/1,612,258 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,326
East Asian	0.00447%	22,368
European (non-Finnish)	0.000933%	107,175

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: DLGAP5
Protein: p.Arg151Trp
Coding: c.451C>T
MANE Select: NM_014750
Type: single nucleotide variant
Location: chr14:55182414 (GRCh38)
Gene constraint: LOEUF 1.112 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 56.52 · 4 PDB

Full DLGAP5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLG1 p.His120Arg Uncertain significance ★★ ⚠ same type
DLG1 p.Ala262= Benign ★★ same type
DLG1 p.Asp633Glu Benign ★★ same type
DLG1 p.Ser470= Benign ★★ same type
DLG1 p.Val167= Benign ★★ same type
DLGAP5 c.1049+7A>C Benign ★★ same type
DLGAP5 c.2064-1G>A Likely pathogenic ★ same type
DLG1 c.484-11849C>T 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/dlgap5-p-arg151trp (accessed [today's date]).

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