Is DAP p.Pro72Leu (c.215C>T) pathogenic?

DAP p.Pro72Leu (c.215C>T) is classified Uncertain significance in DAP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-06). AlphaMissense: likely pathogenic (0.8346); Very rare (popmax 0.00176%, nfe).

How common is DAP p.Pro72Leu (c.215C>T) in the general population?

DAP p.Pro72Leu (c.215C>T) is very rare (popmax 0.00176%, nfe) (gnomAD).

What do computational predictors say about DAP p.Pro72Leu (c.215C>T)?

AlphaMissense predicts likely pathogenic (score 0.8346) — an in-silico prediction, not a clinical call.

DAP p.Pro72Leu

c.215C>T · rs1409337925 · VCV3080050

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8346 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00176%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8346	likely pathogenic
REVEL	0.319	indeterminate
SaProt	LLR -6.44	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 1.1, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 80 kb · p 0.018 · regional, not allelic
Overall
CADD	29.5	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 0.00176% European (non-Finnish) · 20/1,134,306 alleles

Filtering AF 0.00115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000936%

Overall 0.00139% 21/1,516,220 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00176%	56,715
African / African-American	0.00139%	72,102

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.Pro72Leu
Coding: c.215C>T
MANE Select: NM_004394
dbSNP: rs1409337925
Type: single nucleotide variant
Location: chr5:10681150 (GRCh38)
Gene constraint: LOEUF 1.289 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.92
Residue 72: 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-pro72leu (accessed [today's date]).

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