Is FASTKD2 p.Ser571= (c.1713G>A) pathogenic?

FASTKD2 p.Ser571= (c.1713G>A) is classified Likely benign in FASTKD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-17). Very rare (popmax 0.00935%, afr).

How common is FASTKD2 p.Ser571= (c.1713G>A) in the general population?

FASTKD2 p.Ser571= (c.1713G>A) is very rare (popmax 0.00935%, afr) (gnomAD).

FASTKD2 p.Ser571=

c.1713G>A · rs762505449 · VCV1924650

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -8.8	GERP -3.2
Overall
CADD	0.083	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00935% African / African-American · 7/74,872 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00229% 37/1,613,648 alleles · very rare exomes 28/1,461,562 · genomes 9/152,086 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0266%	3,764
African / African-Americangrpmax	0.00935%	10,696
East Asian	0.00446%	22,428
Admixed American	0.00333%	29,989
Remaining individualsnot grpmax-eligible	0.0032%	31,230
South Asian	0.0011%	91,080
European (non-Finnish)	0.000509%	196,636

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: FASTKD2
Protein: p.Ser571=
Coding: c.1713G>A
MANE Select: NM_001136193
dbSNP: rs762505449
Type: single nucleotide variant
Location: chr2:206788055 (GRCh38)
Gene constraint: LOEUF 1.203 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.39
Residue 571: a UniProt-annotated variant site (in coxpd44; decreased mitochondrial large ribosomal subunit assembly); a UniProt-annotated variant site (in coxpd44)

Full FASTKD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FASTKD2 c.882-1G>A Pathogenic/Likely pathogenic ★★ same type
FASTKD2 c.991-2A>G Likely pathogenic ★★ same type
FASTKD2 p.Arg290Ter Pathogenic ★★ same type
FASTKD2 p.Arg358Ter Pathogenic/Likely pathogenic ★★ same type
FASTKD2 p.Arg432Ter Pathogenic/Likely pathogenic ★★ same type
FASTKD2 p.Cys283Ter Pathogenic/Likely pathogenic ★★ same type
FASTKD2 p.Gln564Ter Pathogenic/Likely pathogenic ★★ same type
FASTKD2 p.Trp302Ter 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/fastkd2-p-ser571 (accessed [today's date]).

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