Is PSEN2 p.Ser147= (c.441C>T) pathogenic?

PSEN2 p.Ser147= (c.441C>T) is classified Benign/Likely benign in PSEN2 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-01-19). Low-frequency (popmax 4.78%, afr); Associated with dilated cardiomyopathy 1V.

What condition is associated with PSEN2 p.Ser147= (c.441C>T)?

PSEN2 p.Ser147= (c.441C>T) is associated with dilated cardiomyopathy 1V, Alzheimer disease 4 (ClinVar).

How common is PSEN2 p.Ser147= (c.441C>T) in the general population?

PSEN2 p.Ser147= (c.441C>T) is low-frequency (popmax 4.78%, afr) (gnomAD).

How is Familial isolated dilated cardiomyopathy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

PSEN2 p.Ser147=

c.441C>T · rs114334281 · VCV256183

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.78%, afr)

Conditions

dilated cardiomyopathy 1V

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 -3.9	GERP -3.7
Overall
CADD	7.566	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.78% African / African-American · 3,581/74,978 alleles

Filtering AF 4.65% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.59%

Overall 0.256% 4,135/1,613,304 alleles · low-frequency exomes 2,095/1,461,116 · genomes 2,040/152,188 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.78%	21
Admixed American	0.322%	311
Remaining individualsnot grpmax-eligible	0.315%	317
Middle Eastern	0.099%	1,010
European (non-Finnish)	0.0125%	7,973
South Asian	0.00879%	11,383
East Asian	0.00446%	22,434

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: PSEN2
Protein: p.Ser147=
Coding: c.441C>T
MANE Select: NM_000447
dbSNP: rs114334281
Type: single nucleotide variant
Location: chr1:226885622 (GRCh38)
Gene constraint: LOEUF 0.85 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.99 · 2 PDB

Full PSEN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dilated cardiomyopathy 1V — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Alzheimer disease 4

For Familial isolated dilated cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

PSEN2 p.Asn141Ile Pathogenic ★★ same condition
PSEN2 p.Thr122Pro Pathogenic/Likely pathogenic ★★ same condition
PSEN2 c.*20G>A Uncertain significance ★★ same condition
PSEN2 p.Ala258Thr Uncertain significance ★★ ⚠ same condition
PSEN2 p.Ala291Val Uncertain significance ★★ ⚠ same condition
PSEN2 p.Arg110Cys Uncertain significance ★★ ⚠ same condition
PSEN2 p.Arg29Cys Uncertain significance ★★ ⚠ same condition
PSEN2 p.Arg435Gln Uncertain significance ★★ ⚠ same condition

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/psen2-p-ser147 (accessed [today's date]).

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