Is DAP3 p.Ser308Leu (c.923C>T) pathogenic?

DAP3 p.Ser308Leu (c.923C>T) is classified Likely benign in DAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.0494); Ultra-rare (popmax 0.0161%, afr).

How common is DAP3 p.Ser308Leu (c.923C>T) in the general population?

DAP3 p.Ser308Leu (c.923C>T) is ultra-rare (popmax 0.0161%, afr) (gnomAD).

What do computational predictors say about DAP3 p.Ser308Leu (c.923C>T)?

AlphaMissense predicts likely benign (score 0.0494) — an in-silico prediction, not a clinical call.

DAP3 p.Ser308Leu

c.923C>T · VCV4658444

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0494 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0161%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0494	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -7.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.41 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.5	GERP -0.043, phastCons 0.97
Regional constraint	o/e 0.95	unconstrained · MANE · 28 kb · p 0.25 · regional, not allelic
Overall
CADD	17.67	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 0.0161% African / African-American · 12/74,758 alleles

Filtering AF 0.00923% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00723%

Overall 0.0013% 21/1,610,814 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0161%	6,230
Remaining individualsnot grpmax-eligible	0.00321%	31,161
South Asian	0.00222%	45,138
European (non-Finnish)	0.000424%	235,740

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: DAP3
Protein: p.Ser308Leu
Coding: c.923C>T
MANE Select: NM_004632
Type: single nucleotide variant
Location: chr1:155731963 (GRCh38)
Gene constraint: LOEUF 0.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.23 · 86 PDB
Residue 308: a β-strand

Full DAP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

YY1AP1 c.-151-185G>A Uncertain significance ★★ same type
DAP3 p.Arg20Cys Likely benign ★★ same type
DAP3 p.Val240Phe Benign ★★ same type
YY1AP1 c.-151-68T>C Benign/Likely benign ★★ same type
YY1AP1 c.-30C>T Benign ★★ same type
YY1AP1 c.-49T>C Benign ★★ same type
YY1AP1 c.-60T>C Benign/Likely benign ★★ same type
YY1AP1 c.-95G>A Benign ★★ 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/dap3-p-ser308leu (accessed [today's date]).

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