Is ENC1 p.Ser11Phe (c.32C>T) pathogenic?

ENC1 p.Ser11Phe (c.32C>T) is classified Uncertain significance in ENC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-02). AlphaMissense: ambiguous (0.5265); Absent from gnomAD v4.1.

How common is ENC1 p.Ser11Phe (c.32C>T) in the general population?

ENC1 p.Ser11Phe (c.32C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ENC1 p.Ser11Phe (c.32C>T)?

AlphaMissense predicts ambiguous (score 0.5265) — an in-silico prediction, not a clinical call.

ENC1 p.Ser11Phe

c.32C>T · VCV4248963

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5265 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5265	ambiguous
REVEL	0.477	indeterminate
SaProt	LLR -8.77	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 1,766 bp · p 1.8e-21 · regional, not allelic
Overall
CADD	28.3	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: ENC1
Protein: p.Ser11Phe
Coding: c.32C>T
MANE Select: NM_003633
Type: single nucleotide variant
Location: chr5:74636454 (GRCh38)
Gene constraint: LOEUF 0.653 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 88.22

Full ENC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ENC1 c.-5A>G Benign ★★ same type
ENC1 p.Ala52Val Uncertain significance ★ ⚠ same type
ENC1 p.Arg133Trp Uncertain significance ★ ⚠ same type
ENC1 p.Arg180Thr Uncertain significance ★ ⚠ same type
ENC1 p.Arg225His Uncertain significance ★ ⚠ same type
ENC1 p.Arg289Gln Uncertain significance ★ ⚠ same type
ENC1 p.Arg69His Uncertain significance ★ ⚠ same type
ENC1 p.Arg9His 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/enc1-p-ser11phe (accessed [today's date]).

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