Is DAD1 p.Ser4Trp (c.11C>G) pathogenic?

DAD1 p.Ser4Trp (c.11C>G) is classified Uncertain significance in DAD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-05). AlphaMissense: ambiguous (0.505); Absent from gnomAD v4.1.

How common is DAD1 p.Ser4Trp (c.11C>G) in the general population?

DAD1 p.Ser4Trp (c.11C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DAD1 p.Ser4Trp (c.11C>G)?

AlphaMissense predicts ambiguous (score 0.505) — an in-silico prediction, not a clinical call.

DAD1 p.Ser4Trp

c.11C>G · rs757044016 · VCV2609482

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.505 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.505	ambiguous
REVEL	0.317	indeterminate
SaProt	LLR -16.31	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 14 kb · p 0.12 · regional, not allelic
Overall
CADD	27.4	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: DAD1
Protein: p.Ser4Trp
Coding: c.11C>G
MANE Select: NM_001344
dbSNP: rs757044016
Type: single nucleotide variant
Location: chr14:22589147 (GRCh38)
Gene constraint: LOEUF 0.958 · pLI 0.29 (gnomAD)
Structure: AlphaFold pLDDT 95.43 · 6 PDB

Full DAD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DAD1 c.212-128T>C Benign ★★ same type
DAD1 c.*44+172T>C Benign ★★ same type
DAD1 c.*44+72A>T Benign ★★ same type
DAD1 p.Ter114= Benign ★★ same type
DAD1 p.Ala93Asp Uncertain significance ★ ⚠ same type
DAD1 p.Ala93Gly Uncertain significance ★ ⚠ same type
DAD1 p.Asn54Lys Uncertain significance ★ ⚠ same type
DAD1 p.Cys45Arg 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/dad1-p-ser4trp (accessed [today's date]).

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