Is KY p.Cys634Phe (c.1901G>T) pathogenic?

KY p.Cys634Phe (c.1901G>T) is classified Uncertain significance in KY (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-19). AlphaMissense: ambiguous (0.3983); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with KY p.Cys634Phe (c.1901G>T)?

KY p.Cys634Phe (c.1901G>T) is associated with Inborn genetic diseases, myofibrillar myopathy 7 (ClinVar).

How common is KY p.Cys634Phe (c.1901G>T) in the general population?

KY p.Cys634Phe (c.1901G>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about KY p.Cys634Phe (c.1901G>T)?

AlphaMissense predicts ambiguous (score 0.3983) — an in-silico prediction, not a clinical call.

KY p.Cys634Phe

c.1901G>T · rs1012857901 · VCV1032559

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3983 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.3983	ambiguous
REVEL	0.235	benign-leaning
SaProt	LLR -9.11	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 24 kb · p 7.9e-07 · regional, not allelic
Overall
CADD	25.8	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

Grpmax group 0.00267% African / African-American · 2/74,948 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00161% 26/1,613,572 alleles · very rare exomes 25/1,461,324 · genomes 1/152,248 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,474
European (non-Finnish)	0.00195%	51,293
Remaining individualsnot grpmax-eligible	0.0016%	62,450

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: KY
Protein: p.Cys634Phe
Coding: c.1901G>T
MANE Select: NM_178554
dbSNP: rs1012857901
Type: single nucleotide variant
Location: chr3:134603664 (GRCh38)

Full KY 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

Also linked: myofibrillar myopathy 7

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/ky-p-cys634phe (accessed [today's date]).

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