Is DAD1 p.Ser10Leu (c.29C>T) pathogenic?

DAD1 p.Ser10Leu (c.29C>T) is classified Uncertain significance in DAD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-17). AlphaMissense: likely benign (0.1587); Very rare (popmax 0.00133%, afr).

How common is DAD1 p.Ser10Leu (c.29C>T) in the general population?

DAD1 p.Ser10Leu (c.29C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about DAD1 p.Ser10Leu (c.29C>T)?

AlphaMissense predicts likely benign (score 0.1587) — an in-silico prediction, not a clinical call.

DAD1 p.Ser10Leu

c.29C>T · VCV4237475

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1587 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1587	likely benign
REVEL	0.324	indeterminate
SaProt	LLR -8.87	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 14 kb · p 0.12 · regional, not allelic
Overall
CADD	22.7	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 0.00133% African / African-American · 1/75,042 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000205% 3/1,461,884 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,042
European (non-Finnish)	0.000169%	590,019

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: DAD1
Protein: p.Ser10Leu
Coding: c.29C>T
MANE Select: NM_001344
Type: single nucleotide variant
Location: chr14:22589129 (GRCh38)
Gene constraint: LOEUF 0.958 · pLI 0.29 (gnomAD)
Structure: AlphaFold pLDDT 95.43 · 6 PDB
Residue 10: an α-helix

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-ser10leu (accessed [today's date]).

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