Is FECH p.Gly55Ser (c.163G>A) pathogenic?

FECH p.Gly55Ser (c.163G>A) is classified Benign/Likely benign in FECH (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0655); Rare (popmax 0.918%, afr).

How common is FECH p.Gly55Ser (c.163G>A) in the general population?

FECH p.Gly55Ser (c.163G>A) is rare (popmax 0.918%, afr) (gnomAD).

What do computational predictors say about FECH p.Gly55Ser (c.163G>A)?

AlphaMissense predicts likely benign (score 0.0655) — an in-silico prediction, not a clinical call.

FECH p.Gly55Ser

c.163G>A · rs3848519 · VCV1599190

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0655 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.918%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0655	likely benign
REVEL	0.251	benign-leaning
SaProt	LLR -5.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.9	GERP -3.4, phastCons 0.062
Regional constraint	o/e 0.81	unconstrained · MANE · 36 kb · p 2e-05 · regional, not allelic
Overall
CADD	0.436	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 0.918% African / African-American · 688/74,980 alleles

Filtering AF 0.861% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.838%

Overall 0.0485% 783/1,613,984 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.918%	109
Middle Eastern	0.0828%	1,208
Remaining individualsnot grpmax-eligible	0.0736%	1,359
Admixed American	0.0533%	1,875
South Asian	0.0022%	45,529
European (non-Finnish)	0.000847%	118,002

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.Gly55Ser
Coding: c.163G>A
MANE Select: NM_000140
dbSNP: rs3848519
Type: single nucleotide variant
Location: chr18:57580104 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.37 · 25 PDB
Residue 55: a UniProt-annotated variant site (in epp1)

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

Similar variants

FECH p.Gly55Cys Benign/Likely benign ★★ same residue
FECH c.1137+3A>G Pathogenic/Likely pathogenic ★★ same type
FECH c.314+2T>G Pathogenic/Likely pathogenic ★★ same type
FECH c.463+1G>C Pathogenic ★★ same type
FECH c.598+1G>T Pathogenic ★★ same type
FECH c.599-2A>G Pathogenic ★★ same type
FECH c.913-2A>G Likely pathogenic ★★ same type
FECH p.Arg115Ter Pathogenic/Likely pathogenic ★★ 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/fech-p-gly55ser (accessed [today's date]).

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