Is CPD p.Ser391Phe (c.1172C>T) pathogenic?

CPD p.Ser391Phe (c.1172C>T) is classified Uncertain significance in CPD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-14). AlphaMissense: likely benign (0.1479); Ultra-rare (popmax 0.045%, sas).

How common is CPD p.Ser391Phe (c.1172C>T) in the general population?

CPD p.Ser391Phe (c.1172C>T) is ultra-rare (popmax 0.045%, sas) (gnomAD).

What do computational predictors say about CPD p.Ser391Phe (c.1172C>T)?

AlphaMissense predicts likely benign (score 0.1479) — an in-silico prediction, not a clinical call.

CPD p.Ser391Phe

c.1172C>T · rs761294131 · VCV2223399

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1479 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.045%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1479	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -5.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -1.9, phastCons 0.56
Overall
CADD	21.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.045% South Asian · 41/91,034 alleles

Filtering AF 0.0341% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0302%

Overall 0.00341% 55/1,613,728 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.045%	2,220
Remaining individualsnot grpmax-eligible	0.0064%	15,621
European (non-Finnish)	0.000848%	117,976

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: CPD
Protein: p.Ser391Phe
Coding: c.1172C>T
MANE Select: NM_004839 · reported on NM_001304
dbSNP: rs761294131
Type: single nucleotide variant
Location: chr17:30421698 (GRCh38)
Structure: AlphaFold pLDDT 89.20

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

Similar variants

HOMER2 p.Arg208Cys Uncertain significance ★★ ⚠ same type
HOMER2 p.Arg213Trp Uncertain significance ★★ ⚠ same type
HOMER2 p.Arg215His Uncertain significance ★★ ⚠ same type
HOMER2 p.Arg309Cys Uncertain significance ★★ ⚠ same type
HOMER2 p.Arg334Gln Uncertain significance ★★ ⚠ same type
HOMER2 p.Asn235Lys Uncertain significance ★★ ⚠ same type
HOMER2 p.Glu255Asp Uncertain significance ★★ ⚠ same type
HOMER2 p.Glu274Lys 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/cpd-p-ser391phe (accessed [today's date]).

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