Is DAD1 p.Ter114= (c.341G>A) pathogenic?

DAD1 p.Ter114= (c.341G>A) is classified Benign in DAD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-06-09). Common (popmax 22.9%, afr) — too common for a highly-penetrant pathogenic allele.

DAD1 p.Ter114=

Q: How common is DAD1 p.Ter114= (c.341G>A) in the general population?

DAD1 p.Ter114= (c.341G>A) is common (popmax 22.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.341G>A · rs1051154 · VCV1246525

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Common

common (popmax 22.9%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 0.99, phastCons 1
Overall
CADD	12.76	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 22.9% African / African-American · 17,158/74,954 alleles

Filtering AF 22.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 22.5%

Overall 5% 80,676/1,613,616 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	22.9%	4
Middle Eastern	7.53%	13
Remaining individualsnot grpmax-eligible	5.34%	19
Ashkenazi Jewishnot grpmax-eligible	5.08%	20
Amishnot grpmax-eligible	5.04%	20
European (non-Finnish)	4.32%	23
Finnishnot grpmax-eligible	4.19%	24
Admixed American	4.11%	24
South Asian	2.26%	44
East Asian	0.0111%	8,974

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.Ter114=
Coding: c.341G>A
MANE Select: NM_001344
dbSNP: rs1051154
Type: single nucleotide variant
Location: chr14:22575104 (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.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
DAD1 p.Gln22Arg 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-ter114 (accessed [today's date]).

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