Is ERRFI1 p.Phe411Ser (c.1232T>C) pathogenic?

ERRFI1 p.Phe411Ser (c.1232T>C) is classified Uncertain significance in ERRFI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-27). AlphaMissense: likely pathogenic (0.8442); Absent from gnomAD v4.1.

How common is ERRFI1 p.Phe411Ser (c.1232T>C) in the general population?

ERRFI1 p.Phe411Ser (c.1232T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ERRFI1 p.Phe411Ser (c.1232T>C)?

AlphaMissense predicts likely pathogenic (score 0.8442) — an in-silico prediction, not a clinical call.

ERRFI1 p.Phe411Ser

c.1232T>C · rs1187045234 · VCV2339405

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8442 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8442	likely pathogenic
REVEL	0.29	benign-leaning
SaProt	LLR -9.24	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 11	GERP 2, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 2,406 bp · p 0.00016 · regional, not allelic
Overall
CADD	26.0	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: ERRFI1
Protein: p.Phe411Ser
Coding: c.1232T>C
MANE Select: NM_018948
dbSNP: rs1187045234
Type: single nucleotide variant
Location: chr1:8013367 (GRCh38)
Gene constraint: LOEUF 1.088 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 57.20 · 7 PDB

Full ERRFI1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERRFI1 p.Arg244= Benign ★★ same type
ERRFI1 p.Ile158Leu Benign ★★ same type
ERRFI1 p.Pro239Leu Benign ★★ same type
ERRFI1 p.Ala4Val Uncertain significance ★ ⚠ same type
ERRFI1 p.Ala8Thr Uncertain significance ★ ⚠ same type
ERRFI1 p.Arg148Trp Uncertain significance ★ ⚠ same type
ERRFI1 p.Arg245Lys Uncertain significance ★ ⚠ same type
ERRFI1 p.Arg331Cys 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/errfi1-p-phe411ser (accessed [today's date]).

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