Is TKFC p.Gly192= (c.576G>A) pathogenic?

TKFC p.Gly192= (c.576G>A) is classified Benign in TKFC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-01). Low-frequency (popmax 1.57%, nfe).

How common is TKFC p.Gly192= (c.576G>A) in the general population?

TKFC p.Gly192= (c.576G>A) is low-frequency (popmax 1.57%, nfe) (gnomAD).

TKFC p.Gly192=

c.576G>A · rs117064389 · VCV2641824

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.57%, nfe)

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 -0.18	GERP -4, phastCons 0.015
Overall
CADD	7.451	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.57% European (non-Finnish) · 18,529/1,179,842 alleles

Filtering AF 1.55% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.54%

Overall 1.24% 19,971/1,613,880 alleles · low-frequency exomes 18,640/1,461,662 · genomes 1,331/152,218 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	9.21%	11
European (non-Finnish)grpmax	1.57%	64
Remaining individualsnot grpmax-eligible	0.819%	122
Finnishnot grpmax-eligible	0.497%	201
Middle Eastern	0.413%	242
Admixed American	0.317%	316
African / African-American	0.221%	452
Ashkenazi Jewishnot grpmax-eligible	0.132%	759
South Asian	0.119%	843

Amish 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: TKFC
Protein: p.Gly192=
Coding: c.576G>A
MANE Select: NM_015533
dbSNP: rs117064389
Type: single nucleotide variant
Location: chr11:61341833 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.40
Residue 192: the dhak domain

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

Similar variants

TKFC p.Arg543Ile Likely pathogenic ★★ same type
TKFC p.Arg228Gln Uncertain significance ★★ ⚠ same type
TKFC p.Asp403Asn Uncertain significance ★★ ⚠ same type
TKFC p.Gln257Pro Uncertain significance ★★ ⚠ same type
TKFC c.194-13C>T Benign ★★ same type
TKFC c.775+39A>C Benign ★★ same type
TKFC p.Ala185Thr Benign ★★ same type
TKFC p.Thr157= Benign ★★ 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/tkfc-p-gly192 (accessed [today's date]).

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