Is FASTKD2 p.Phe234Leu (c.700T>C) pathogenic?

FASTKD2 p.Phe234Leu (c.700T>C) is classified Uncertain significance in FASTKD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-27). AlphaMissense: likely pathogenic (0.8176); No allele count reported in gnomAD v4.1 (AN 1,613,860); Associated with Inborn genetic diseases.

What condition is associated with FASTKD2 p.Phe234Leu (c.700T>C)?

FASTKD2 p.Phe234Leu (c.700T>C) is associated with Inborn genetic diseases (ClinVar).

How common is FASTKD2 p.Phe234Leu (c.700T>C) in the general population?

FASTKD2 p.Phe234Leu (c.700T>C) is no allele count reported in gnomAD v4.1 (AN 1,613,860) (gnomAD).

What do computational predictors say about FASTKD2 p.Phe234Leu (c.700T>C)?

AlphaMissense predicts likely pathogenic (score 0.8176) — an in-silico prediction, not a clinical call.

FASTKD2 p.Phe234Leu

c.700T>C · VCV4619668

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8176 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,860)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8176	likely pathogenic · top 6% in FASTKD2
REVEL	0.308	indeterminate
SaProt	LLR -5.70	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 25 kb · p 0.12 · regional, not allelic
Overall
CADD	23.2	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

No allele count reported in gnomAD v4.1 (AN 1,613,860). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FASTKD2
Protein: p.Phe234Leu
Coding: c.700T>C
MANE Select: NM_001136193
Type: single nucleotide variant
Location: chr2:206767393 (GRCh38)
Gene constraint: LOEUF 1.203 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.39
Residue 234: a UniProt-annotated variant site (in coxpd44)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FASTKD2 p.Ala187Val Uncertain significance ★★ ⚠ same condition
FASTKD2 p.Arg102Gly Uncertain significance ★★ ⚠ same condition
FASTKD2 p.Arg261Cys Uncertain significance ★★ same condition
FASTKD2 p.Arg327Gly Uncertain significance ★★ ⚠ same condition
FASTKD2 p.Asp412Asn Uncertain significance ★★ ⚠ same condition
FASTKD2 p.Asp544His Uncertain significance ★★ ⚠ same condition
FASTKD2 p.Asp72Gly Uncertain significance ★★ ⚠ same condition
FASTKD2 p.Glu278Lys Uncertain significance ★★ ⚠ same condition

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-phe234leu (accessed [today's date]).

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