Is TKFC p.Gly56Val (c.167G>T) pathogenic?

TKFC p.Gly56Val (c.167G>T) is classified Uncertain significance in TKFC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-28). AlphaMissense: likely pathogenic (0.9731); Very rare (popmax 0.00508%, amr).

How common is TKFC p.Gly56Val (c.167G>T) in the general population?

TKFC p.Gly56Val (c.167G>T) is very rare (popmax 0.00508%, amr) (gnomAD).

What do computational predictors say about TKFC p.Gly56Val (c.167G>T)?

AlphaMissense predicts likely pathogenic (score 0.9731) — an in-silico prediction, not a clinical call.

TKFC p.Gly56Val

c.167G>T · rs763703269 · VCV2520746

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9731 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00508%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9731	likely pathogenic · top 6% in TKFC
REVEL	0.877	moderately pathogenic-leaning
SaProt	LLR -13.77	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.3, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 12 kb · p 0.025 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00508% Admixed American · 3/59,088 alleles

Filtering AF 0.00135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000674%

Overall 0.000997% 16/1,604,108 alleles · very rare exomes 14/1,451,900 · genomes 2/152,208 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00508%	19,696
Remaining individualsnot grpmax-eligible	0.00321%	31,109
European (non-Finnish)	0.000934%	107,091

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.Gly56Val
Coding: c.167G>T
MANE Select: NM_015533
dbSNP: rs763703269
Type: single nucleotide variant
Location: chr11:61338104 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.40
Residue 56: the dhak domain; a binding site

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-gly56val (accessed [today's date]).

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