Is ENTHD1 p.Pro369fs (c.1104_1105del) pathogenic?

ENTHD1 p.Pro369fs (c.11041105del) is classified Likely benign in ENTHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-01). Rare (popmax 0.84%, nfe).

How common is ENTHD1 p.Pro369fs (c.1104_1105del) in the general population?

ENTHD1 p.Pro369fs (c.1104_1105del) is rare (popmax 0.84%, nfe) (gnomAD).

ENTHD1 p.Pro369fs

c.1104_1105del · VCV4533407

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.84%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Overall
CADD	29.7	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 0.84% European (non-Finnish) · 9,910/1,179,934 alleles

Filtering AF 0.826% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.82%

Overall 0.688% 11,111/1,613,872 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.892%	112
European (non-Finnish)grpmax	0.84%	119
Remaining individualsnot grpmax-eligible	0.507%	197
Middle Eastern	0.165%	606
African / African-American	0.136%	735
South Asian	0.126%	792
Admixed American	0.117%	856
Ashkenazi Jewishnot grpmax-eligible	0.0507%	1,974
East Asian	0.00223%	44,864

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ENTHD1
Protein: p.Pro369fs
Coding: c.1104_1105del
MANE Select: NM_152512
Type: Microsatellite
Location: chr22:39765337 (GRCh38)
Gene constraint: LOEUF 0.928 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.58

Full ENTHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/enthd1-p-pro369fs (accessed [today's date]).

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