Is ENOSF1 p.Cys385Phe (c.1154G>T) pathogenic?

ENOSF1 p.Cys385Phe (c.1154G>T) is classified Uncertain significance in ENOSF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely pathogenic (0.7412); Absent from gnomAD v4.1.

How common is ENOSF1 p.Cys385Phe (c.1154G>T) in the general population?

ENOSF1 p.Cys385Phe (c.1154G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ENOSF1 p.Cys385Phe (c.1154G>T)?

AlphaMissense predicts likely pathogenic (score 0.7412) — an in-silico prediction, not a clinical call.

ENOSF1 p.Cys385Phe

c.1154G>T · VCV4664348

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7412 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7412	likely pathogenic
REVEL	0.284	benign-leaning
SaProt	LLR -3.92	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.9, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 38 kb · p 0.14 · regional, not allelic
Overall
CADD	26.5	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: ENOSF1
Protein: p.Cys385Phe
Coding: c.1154G>T
MANE Select: NM_017512
Type: single nucleotide variant
Location: chr18:675397 (GRCh38)
Gene constraint: LOEUF 1.236 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.47 · 1 PDB
Residue 385: a β-strand

Full ENOSF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ENOSF1 c.*1219T>C Benign ★★ same type
TYMS c.556+1G>A Pathogenic ★ same type
TYMS p.Arg271Ter Pathogenic ★ same type
ENOSF1 c.84+108G>C Uncertain significance ★ same type
ENOSF1 c.84+112A>C Uncertain significance ★ same type
ENOSF1 c.84+114C>G Uncertain significance ★ same type
ENOSF1 c.84+125T>C Uncertain significance ★ same type
ENOSF1 c.84+130A>C 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/enosf1-p-cys385phe (accessed [today's date]).

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