Is PHYKPL p.Val323Ile (c.967G>A) pathogenic?

PHYKPL p.Val323Ile (c.967G>A) is classified Uncertain significance in PHYKPL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-27). AlphaMissense: likely benign (0.2046); Ultra-rare (popmax 0.0254%, afr).

How common is PHYKPL p.Val323Ile (c.967G>A) in the general population?

PHYKPL p.Val323Ile (c.967G>A) is ultra-rare (popmax 0.0254%, afr) (gnomAD).

What do computational predictors say about PHYKPL p.Val323Ile (c.967G>A)?

AlphaMissense predicts likely benign (score 0.2046) — an in-silico prediction, not a clinical call.

PHYKPL p.Val323Ile

c.967G>A · rs375319327 · VCV2377787

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2046 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0254%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2046	likely benign
REVEL	0.317	indeterminate
SaProt	LLR -10.77	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 21 kb · p 0.0047 · regional, not allelic
Overall
CADD	28.2	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 0.0254% African / African-American · 19/74,892 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00651% 105/1,613,764 alleles · ultra-rare exomes 90/1,461,588 · genomes 15/152,176 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0254%	3,942
European (non-Finnish)	0.00695%	14,390
East Asian	0.00445%	22,448
Admixed American	0.00167%	59,988
Remaining individualsnot grpmax-eligible	0.0016%	62,462

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.Val323Ile
Coding: c.967G>A
MANE Select: NM_153373
dbSNP: rs375319327
Type: single nucleotide variant
Location: chr5:178215391 (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.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
PHYKPL p.Arg125His 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-val323ile (accessed [today's date]).

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