Is DAP p.Phe70Ile (c.208T>A) pathogenic?

DAP p.Phe70Ile (c.208T>A) is classified Uncertain significance in DAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-13). AlphaMissense: likely pathogenic (0.9949); Ultra-rare (popmax 0.057%, afr).

How common is DAP p.Phe70Ile (c.208T>A) in the general population?

DAP p.Phe70Ile (c.208T>A) is ultra-rare (popmax 0.057%, afr) (gnomAD).

What do computational predictors say about DAP p.Phe70Ile (c.208T>A)?

AlphaMissense predicts likely pathogenic (score 0.9949) — an in-silico prediction, not a clinical call.

DAP p.Phe70Ile

c.208T>A · VCV3838235

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9949 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.057%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9949	likely pathogenic
REVEL	0.414	indeterminate
SaProt	LLR -5.33	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 11	GERP 1, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 80 kb · p 0.018 · regional, not allelic
Overall
CADD	26.2	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 0.057% African / African-American · 41/71,964 alleles

Filtering AF 0.0431% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0383%

Overall 0.00311% 47/1,510,356 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.057%	1,755
Remaining individualsnot grpmax-eligible	0.00517%	19,332
Admixed American	0.00467%	21,402
European (non-Finnish)	8.84e-05%	1,131,484

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.Phe70Ile
Coding: c.208T>A
MANE Select: NM_004394
Type: single nucleotide variant
Location: chr5:10681157 (GRCh38)
Gene constraint: LOEUF 1.289 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.92
Residue 70: 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-phe70ile (accessed [today's date]).

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