Is FECH p.Gly16Asp (c.47G>A) pathogenic?

FECH p.Gly16Asp (c.47G>A) is classified Uncertain significance in FECH (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-27). AlphaMissense: likely benign (0.2107); Ultra-rare (popmax 0.0346%, mid); Associated with Inborn genetic diseases.

What condition is associated with FECH p.Gly16Asp (c.47G>A)?

FECH p.Gly16Asp (c.47G>A) is associated with Inborn genetic diseases (ClinVar).

How common is FECH p.Gly16Asp (c.47G>A) in the general population?

FECH p.Gly16Asp (c.47G>A) is ultra-rare (popmax 0.0346%, mid) (gnomAD).

What do computational predictors say about FECH p.Gly16Asp (c.47G>A)?

AlphaMissense predicts likely benign (score 0.2107) — an in-silico prediction, not a clinical call.

FECH p.Gly16Asp

c.47G>A · rs746234243 · VCV2211641

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2107 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0346%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2107	likely benign
REVEL	0.41	indeterminate
SaProt	LLR -10.41	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.23	GERP 1.3
Regional constraint	o/e 0.81	unconstrained · MANE · 36 kb · p 2e-05 · regional, not allelic
Overall
CADD	17.32	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 0.0346% Middle Eastern · 2/5,782 alleles

Filtering AF 0.00608% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00417%

Overall 0.00473% 72/1,522,390 alleles · ultra-rare exomes 70/1,370,198 · genomes 2/152,192 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0346%	2,891
European (non-Finnish)	0.00569%	17,567
Admixed American	0.00398%	25,127
Remaining individualsnot grpmax-eligible	0.00337%	29,677
South Asian	0.00121%	82,592

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.Gly16Asp
Coding: c.47G>A
MANE Select: NM_000140
dbSNP: rs746234243
Type: single nucleotide variant
Location: chr18:57586574 (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.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.Gly16fs Likely pathogenic ★ same residue

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-gly16asp (accessed [today's date]).

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