Is PHYH p.Val207Ile (c.619G>A) pathogenic?

PHYH p.Val207Ile (c.619G>A) is classified Conflicting classifications of pathogenicity in PHYH (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-10-15). AlphaMissense: likely benign (0.1654); Ultra-rare (popmax 0.0527%, sas).

How common is PHYH p.Val207Ile (c.619G>A) in the general population?

PHYH p.Val207Ile (c.619G>A) is ultra-rare (popmax 0.0527%, sas) (gnomAD).

What do computational predictors say about PHYH p.Val207Ile (c.619G>A)?

AlphaMissense predicts likely benign (score 0.1654) — an in-silico prediction, not a clinical call.

PHYH p.Val207Ile

c.619G>A · rs555663097 · VCV972212

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1654 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0527%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1654	likely benign
REVEL	0.399	indeterminate
SaProt	LLR -6.48	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -0.51, phastCons 0.58
Regional constraint	o/e 0.98	unconstrained · MANE · 22 kb · p 0.67 · regional, not allelic
Overall
CADD	18.19	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 0.0527% South Asian · 48/91,084 alleles

Filtering AF 0.0408% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0366%

Overall 0.0031% 50/1,614,172 alleles · ultra-rare exomes 46/1,461,830 · genomes 4/152,342 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0527%	1,898
Admixed American	0.00167%	60,024
European (non-Finnish)	8.47e-05%	1,180,043

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.Val207Ile
Coding: c.619G>A
MANE Select: NM_006214
dbSNP: rs555663097
Type: single nucleotide variant
Location: chr10:13288419 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.33 · 1 PDB
Residue 207: a β-strand

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

Similar variants

PHYH p.Val207Asp 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
PHYH c.678+2T>C Likely pathogenic ★★ same type
PHYH p.Ala277Glu 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-val207ile (accessed [today's date]).

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