Is GFER p.Asp43= (c.129C>T) pathogenic?

GFER p.Asp43= (c.129C>T) is classified Likely benign in GFER (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-07). Ultra-rare (popmax 0.0329%, afr).

How common is GFER p.Asp43= (c.129C>T) in the general population?

GFER p.Asp43= (c.129C>T) is ultra-rare (popmax 0.0329%, afr) (gnomAD).

GFER p.Asp43=

c.129C>T · rs1016725284 · VCV763653

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.59	GERP -2.4, phastCons 0.91
Overall
CADD	5.518	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% African / African-American · 23/69,984 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.019%

Overall 0.00166% 25/1,508,824 alleles · ultra-rare exomes 13/1,356,626 · genomes 12/152,198 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0329%	3,043
Remaining individualsnot grpmax-eligible	0.00342%	29,281

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: GFER
Protein: p.Asp43=
Coding: c.129C>T
MANE Select: NM_005262
dbSNP: rs1016725284
Type: single nucleotide variant
Location: chr16:1984347 (GRCh38)
Gene constraint: LOEUF 1.87 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.50 · 7 PDB
Residue 43: the 'disordered' region

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

Similar variants

GFER p.Asp43Glu Uncertain significance ★★ ⚠ same residue
GFER p.Asp43Tyr Uncertain significance ★★ ⚠ same residue
GFER p.Arg194His Pathogenic ★★ same type
GFER p.Ser189Ter Pathogenic ★★ same type
GFER c.258+1G>A Uncertain significance ★★ same type
GFER p.Ala45Thr Uncertain significance ★★ ⚠ same type
GFER p.Ala46Val Uncertain significance ★★ ⚠ same type
GFER p.Ala73Ser 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/gfer-p-asp43 (accessed [today's date]).

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