Is FECH p.Leu232Phe (c.694C>T) pathogenic?

FECH p.Leu232Phe (c.694C>T) is classified Uncertain significance in FECH (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-23). AlphaMissense: likely benign (0.1555); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with FECH p.Leu232Phe (c.694C>T)?

FECH p.Leu232Phe (c.694C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FECH p.Leu232Phe (c.694C>T) in the general population?

FECH p.Leu232Phe (c.694C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FECH p.Leu232Phe (c.694C>T)?

AlphaMissense predicts likely benign (score 0.1555) — an in-silico prediction, not a clinical call.

FECH p.Leu232Phe

c.694C>T · VCV4840244

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1555 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1555	likely benign
REVEL	0.742	pathogenic-leaning
SaProt	LLR -9.79	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 36 kb · p 2e-05 · regional, not allelic
Overall
CADD	25.7	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: FECH
Protein: p.Leu232Phe
Coding: c.694C>T
MANE Select: NM_000140
Type: single nucleotide variant
Location: chr18:57562885 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.37 · 25 PDB
Residue 232: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FECH p.Leu4Phe Uncertain significance ★★ ⚠ same condition
FECH p.Lys320Arg Uncertain significance ★★ ⚠ same condition
FECH p.Met267Thr Uncertain significance ★★ ⚠ same condition
FECH p.Ser197Thr Uncertain significance ★★ ⚠ same condition
FECH p.Ser268Phe Uncertain significance ★★ ⚠ same condition
FECH p.Val166Ile Uncertain significance ★★ ⚠ same condition
FECH p.Asn105= Likely benign ★★ same condition
FECH p.Ala10Thr Uncertain significance ★ same condition

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/fech-p-leu232phe (accessed [today's date]).

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