Is DTHD1 p.Ser879fs (c.2635del) pathogenic?

DTHD1 p.Ser879fs (c.2635del) is classified Benign/Likely benign in DTHD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-29). Low-frequency (popmax 1.06%, eas).

How common is DTHD1 p.Ser879fs (c.2635del) in the general population?

DTHD1 p.Ser879fs (c.2635del) is low-frequency (popmax 1.06%, eas) (gnomAD).

DTHD1 p.Ser879fs

c.2635del · rs529758698 · VCV866271

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

low-frequency (popmax 1.06%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (10 of 10) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.4	GERP 1.8, phastCons 0.99
Overall
CADD	25.4	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 1.06% East Asian · 432/40,916 alleles

Filtering AF 0.974% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.941%

Overall 0.0293% 454/1,551,572 alleles · low-frequency exomes 406/1,399,294 · genomes 48/152,278 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.06%	95
Remaining individualsnot grpmax-eligible	0.0233%	4,294
Middle Eastern	0.0167%	5,988
Admixed American	0.00196%	50,986
European (non-Finnish)	0.000523%	191,153

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: DTHD1
Protein: p.Ser879fs
Coding: c.2635del
MANE Select: NM_001170700
dbSNP: rs529758698
Type: Deletion
Location: chr4:36343738 (GRCh38)
Gene constraint: LOEUF 1.034 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.99

Full DTHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DTHD1 p.Gln834_Ile836del Uncertain significance ★★ same type
DTHD1 p.Lys857fs Uncertain significance ★★ same type
DTHD1 p.Asn694fs Uncertain significance ★ same type
DTHD1 p.Asp582fs Uncertain significance ★ same type
DTHD1 p.Glu324fs Uncertain significance ★ same type
DTHD1 p.His849fs Uncertain significance ★ same type
DTHD1 p.Ile379del Uncertain significance ★ same type
DTHD1 p.Lys702fs 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/dthd1-p-ser879fs (accessed [today's date]).

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