Is PHYH p.Ser284Arg (c.850A>C) pathogenic?

PHYH p.Ser284Arg (c.850A>C) is classified Uncertain significance in PHYH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-09). AlphaMissense: ambiguous (0.53); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PHYH p.Ser284Arg (c.850A>C)?

PHYH p.Ser284Arg (c.850A>C) is associated with Inborn genetic diseases (ClinVar).

How common is PHYH p.Ser284Arg (c.850A>C) in the general population?

PHYH p.Ser284Arg (c.850A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PHYH p.Ser284Arg (c.850A>C)?

AlphaMissense predicts ambiguous (score 0.53) — an in-silico prediction, not a clinical call.

PHYH p.Ser284Arg

c.850A>C · VCV4136197

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.53 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.53	ambiguous
REVEL	0.67	pathogenic-leaning
SaProt	LLR -9.59	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.62	GERP -3
Regional constraint	o/e 0.98	unconstrained · MANE · 22 kb · p 0.67 · regional, not allelic
Overall
CADD	18.72	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PHYH
Protein: p.Ser284Arg
Coding: c.850A>C
MANE Select: NM_006214
Type: single nucleotide variant
Location: chr10:13281089 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.33 · 1 PDB
Residue 284: a β-strand

Full PHYH 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

PHYH p.Ala192Ser Uncertain significance ★★ ⚠ same condition
PHYH p.Ala244Gly Uncertain significance ★★ ⚠ same condition
PHYH p.Ala283Thr Uncertain significance ★★ same condition
PHYH p.Arg245Trp Uncertain significance ★★ ⚠ same condition
PHYH p.Arg80Cys Uncertain significance ★★ ⚠ same condition
PHYH p.Asp77Asn Uncertain significance ★★ ⚠ same condition
PHYH p.Gln42Arg Uncertain significance ★★ ⚠ same condition
PHYH p.Glu241Gly 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/phyh-p-ser284arg (accessed [today's date]).

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