Is DAP p.Lys40Arg (c.119A>G) pathogenic?

DAP p.Lys40Arg (c.119A>G) is classified Uncertain significance in DAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-03). AlphaMissense: likely benign (0.0689); Very rare (popmax 0.000254%, nfe).

How common is DAP p.Lys40Arg (c.119A>G) in the general population?

DAP p.Lys40Arg (c.119A>G) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about DAP p.Lys40Arg (c.119A>G)?

AlphaMissense predicts likely benign (score 0.0689) — an in-silico prediction, not a clinical call.

DAP p.Lys40Arg

c.119A>G · VCV3838239

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0689 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0689	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -7.85	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 -0.15	GERP -2.5
Regional constraint	o/e 0.80	unconstrained · MANE · 80 kb · p 0.018 · regional, not allelic
Overall
CADD	14.15	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 0.000254% European (non-Finnish) · 3/1,179,956 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,614,012 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)grpmax	0.000254%	393,318

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DAP
Protein: p.Lys40Arg
Coding: c.119A>G
MANE Select: NM_004394
Type: single nucleotide variant
Location: chr5:10748208 (GRCh38)
Gene constraint: LOEUF 1.289 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.92
Residue 40: the 'disordered' region

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

Similar variants

DAP p.Ala18Ser Uncertain significance ★ ⚠ same type
DAP p.Arg101His Uncertain significance ★ ⚠ same type
DAP p.Arg65Leu Uncertain significance ★ ⚠ same type
DAP p.Arg65Trp 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

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-lys40arg (accessed [today's date]).

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