Is FECH p.Pro67Leu (c.200C>T) pathogenic?

FECH p.Pro67Leu (c.200C>T) is classified Uncertain significance in FECH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-29). AlphaMissense: likely benign (0.2556); Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with FECH p.Pro67Leu (c.200C>T)?

FECH p.Pro67Leu (c.200C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FECH p.Pro67Leu (c.200C>T) in the general population?

FECH p.Pro67Leu (c.200C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about FECH p.Pro67Leu (c.200C>T)?

AlphaMissense predicts likely benign (score 0.2556) — an in-silico prediction, not a clinical call.

FECH p.Pro67Leu

c.200C>T · rs768844837 · VCV3094360

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2556 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2556	likely benign
REVEL	0.523	indeterminate
SaProt	LLR -10.80	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 36 kb · p 2e-05 · regional, not allelic
Overall
CADD	23.0	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

Grpmax group 0.0022% South Asian · 2/91,062 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00116% 17/1,461,810 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,531
European (non-Finnish)	0.00127%	78,666

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: FECH
Protein: p.Pro67Leu
Coding: c.200C>T
MANE Select: NM_000140
dbSNP: rs768844837
Type: single nucleotide variant
Location: chr18:57573360 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.37 · 25 PDB

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.Pro67= Likely benign ★ same residue
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

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-pro67leu (accessed [today's date]).

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