Is DAP p.Arg65Leu (c.194G>T) pathogenic?

DAP p.Arg65Leu (c.194G>T) is classified Uncertain significance in DAP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-28). AlphaMissense: likely pathogenic (0.8841); Absent from gnomAD v4.1.

How common is DAP p.Arg65Leu (c.194G>T) in the general population?

DAP p.Arg65Leu (c.194G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DAP p.Arg65Leu (c.194G>T)?

AlphaMissense predicts likely pathogenic (score 0.8841) — an in-silico prediction, not a clinical call.

DAP p.Arg65Leu

c.194G>T · VCV3838238

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8841 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8841	likely pathogenic
REVEL	0.13	moderately benign-leaning
SaProt	LLR -8.02	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 0.62, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 80 kb · p 0.018 · 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DAP
Protein: p.Arg65Leu
Coding: c.194G>T
MANE Select: NM_004394
Type: single nucleotide variant
Location: chr5:10683530 (GRCh38)
Gene constraint: LOEUF 1.289 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.92
Residue 65: the 'disordered' region

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

Similar variants

DAP p.Arg65Trp Uncertain significance ★ ⚠ same residue
DAP p.Ala18Ser Uncertain significance ★ ⚠ same type
DAP p.Arg101His Uncertain significance ★ ⚠ same type
DAP p.Gln28Arg Uncertain significance ★ ⚠ same type
DAP p.Gln98His Uncertain significance ★ ⚠ same type
DAP p.Glu39Asp Uncertain significance ★ ⚠ same type
DAP p.His79Tyr Uncertain significance ★ ⚠ same type
DAP p.Lys40Arg 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/dap-p-arg65leu (accessed [today's date]).

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