Is PHLPP1 p.Ser641= (c.1923A>C) pathogenic?

PHLPP1 p.Ser641= (c.1923A>C) is classified Likely benign in PHLPP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-01). Rare (popmax 0.373%, nfe).

How common is PHLPP1 p.Ser641= (c.1923A>C) in the general population?

PHLPP1 p.Ser641= (c.1923A>C) is rare (popmax 0.373%, nfe) (gnomAD).

PHLPP1 p.Ser641=

c.1923A>C · rs190711929 · VCV2648791

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.373%, nfe)

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 -1.2	GERP -4.2
Overall
CADD	3.649	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.373% European (non-Finnish) · 4,402/1,179,804 alleles

Filtering AF 0.364% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.36%

Overall 0.361% 5,825/1,613,910 alleles · rare exomes 5,186/1,461,596 · genomes 639/152,314 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.51%	66
Ashkenazi Jewishnot grpmax-eligible	0.733%	136
European (non-Finnish)grpmax	0.373%	268
Remaining individualsnot grpmax-eligible	0.301%	332
Admixed American	0.045%	2,223
Middle Eastern	0.033%	3,031
African / African-American	0.0306%	3,263
South Asian	0.0022%	45,542

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: PHLPP1
Protein: p.Ser641=
Coding: c.1923A>C
MANE Select: NM_194449
dbSNP: rs190711929
Type: single nucleotide variant
Location: chr18:62860458 (GRCh38)
Gene constraint: LOEUF 0.546 · pLI 0.22 (gnomAD)
Structure: AlphaFold pLDDT 66.08

Full PHLPP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PHLPP1 p.Ala876Val Uncertain significance ★★ ⚠ same type
PHLPP1 p.His197= Benign ★★ same type
PHLPP1 p.Phe291Val Benign ★★ same type
PHLPP1 p.Pro1690= Benign ★★ same type
PHLPP1 p.Ala1004Val Uncertain significance ★ ⚠ same type
PHLPP1 p.Ala107Thr Uncertain significance ★ ⚠ same type
PHLPP1 p.Ala112Val Uncertain significance ★ ⚠ same type
PHLPP1 p.Ala1167Thr 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/phlpp1-p-ser641 (accessed [today's date]).

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