Is PHYH p.Ser109= (c.327C>T) pathogenic?

PHYH p.Ser109= (c.327C>T) is classified Likely benign in PHYH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-28). Very rare (popmax 0.00223%, eas).

How common is PHYH p.Ser109= (c.327C>T) in the general population?

PHYH p.Ser109= (c.327C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

PHYH p.Ser109=

c.327C>T · rs774205409 · VCV2781745

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.4	GERP -2.9
Overall
CADD	2.277	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,888 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000806% 13/1,613,742 alleles · very rare exomes 12/1,461,618 · genomes 1/152,124 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00937%	10,669
East Asiangrpmax	0.00223%	44,888
Admixed American	0.00167%	59,988
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	0.000339%	294,949

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser109=
Coding: c.327C>T
MANE Select: NM_006214
dbSNP: rs774205409
Type: single nucleotide variant
Location: chr10:13294515 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.33 · 1 PDB

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

Similar variants

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
PHYH c.678+2T>C Likely pathogenic ★★ same type
PHYH p.Ala277Glu Pathogenic/Likely pathogenic ★★ same type
PHYH p.Arg275Gln 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-ser109 (accessed [today's date]).

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