Is PHYH p.Ala192= (c.576C>T) pathogenic?

PHYH p.Ala192= (c.576C>T) is classified Likely benign in PHYH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-19). Very rare (popmax 0.00667%, amr).

How common is PHYH p.Ala192= (c.576C>T) in the general population?

PHYH p.Ala192= (c.576C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

PHYH p.Ala192=

c.576C>T · rs371154155 · VCV1113198

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

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 -0.63	GERP -3.1
Overall
CADD	1.651	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/60,014 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000558% 9/1,614,130 alleles · very rare exomes 8/1,461,890 · genomes 1/152,240 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,004
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
European (non-Finnish)	0.000339%	295,015

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: PHYH
Protein: p.Ala192=
Coding: c.576C>T
MANE Select: NM_006214
dbSNP: rs371154155
Type: single nucleotide variant
Location: chr10:13288462 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.33 · 1 PDB
Residue 192: a UniProt-annotated variant site (in rd); a β-strand

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

Similar variants

PHYH p.Ala192Ser Uncertain significance ★★ ⚠ same residue
PHYH p.Ala192Thr Uncertain significance ★★ ⚠ same residue
PHYH p.Ala192_Trp193insAla Uncertain significance ★ same residue
PHYH c.134+1G>A Likely pathogenic ★★ same type
PHYH c.135-1G>C Pathogenic/Likely pathogenic ★★ same type
PHYH c.135-2A>G Pathogenic ★★ same type
PHYH c.497-1G>A Likely pathogenic ★★ same type
PHYH c.497-2A>G Pathogenic/Likely pathogenic ★★ 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/phyh-p-ala192 (accessed [today's date]).

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