Is PHYKPL p.Val35= (c.105C>T) pathogenic?

PHYKPL p.Val35= (c.105C>T) is classified Likely benign in PHYKPL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-13). Ultra-rare (popmax 0.015%, amr).

How common is PHYKPL p.Val35= (c.105C>T) in the general population?

PHYKPL p.Val35= (c.105C>T) is ultra-rare (popmax 0.015%, amr) (gnomAD).

PHYKPL p.Val35=

c.105C>T · VCV4973278

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, 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 2.2	GERP -2.3, phastCons 1
Overall
CADD	11.17	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.015% Admixed American · 9/60,002 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.000991% 16/1,614,070 alleles · ultra-rare exomes 9/1,461,882 · genomes 7/152,188 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,667
East Asian	0.00223%	44,898
European (non-Finnish)	0.000508%	196,674

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: PHYKPL
Protein: p.Val35=
Coding: c.105C>T
MANE Select: NM_153373
Type: single nucleotide variant
Location: chr5:178231478 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.20

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

Similar variants

PHYKPL p.Val35Ile Uncertain significance ★ ⚠ same residue
PHYKPL p.Glu437Val Uncertain significance ★★ ⚠ same type
PHYKPL p.Ala139Val Uncertain significance ★ ⚠ same type
PHYKPL p.Ala168Val Uncertain significance ★ ⚠ same type
PHYKPL p.Ala318Thr Uncertain significance ★ ⚠ same type
PHYKPL p.Ala386Ser Uncertain significance ★ ⚠ same type
PHYKPL p.Ala3Pro Uncertain significance ★ ⚠ same type
PHYKPL p.Arg125Cys Uncertain significance ★ ⚠ 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/phykpl-p-val35 (accessed [today's date]).

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