Is ENTHD1 p.Cys93Phe (c.278G>T) pathogenic?

ENTHD1 p.Cys93Phe (c.278G>T) is classified Uncertain significance in ENTHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-03). AlphaMissense: likely pathogenic (0.79); Absent from gnomAD v4.1.

How common is ENTHD1 p.Cys93Phe (c.278G>T) in the general population?

ENTHD1 p.Cys93Phe (c.278G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ENTHD1 p.Cys93Phe (c.278G>T)?

AlphaMissense predicts likely pathogenic (score 0.79) — an in-silico prediction, not a clinical call.

ENTHD1 p.Cys93Phe

c.278G>T · rs2518543405 · VCV2315587

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.79 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.79	likely pathogenic · top 9% in ENTHD1
REVEL	0.43	indeterminate
SaProt	LLR -9.32	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 144 kb · p 0.0022 · regional, not allelic
Overall
CADD	24.8	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: ENTHD1
Protein: p.Cys93Phe
Coding: c.278G>T
MANE Select: NM_152512
dbSNP: rs2518543405
Type: single nucleotide variant
Location: chr22:39887471 (GRCh38)
Gene constraint: LOEUF 0.928 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.58
Residue 93: the enth domain

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

Similar variants

ENTHD1 p.Ala112Ser Uncertain significance ★ ⚠ same type
ENTHD1 p.Ala144Gly Uncertain significance ★ ⚠ same type
ENTHD1 p.Ala170Val Uncertain significance ★ ⚠ same type
ENTHD1 p.Ala385Gly Uncertain significance ★ ⚠ same type
ENTHD1 p.Arg121Trp Uncertain significance ★ ⚠ same type
ENTHD1 p.Arg141Met Uncertain significance ★ ⚠ same type
ENTHD1 p.Arg146Gln Uncertain significance ★ ⚠ same type
ENTHD1 p.Arg160Thr 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/enthd1-p-cys93phe (accessed [today's date]).

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