Is CPD p.Phe197Leu (c.591C>A) pathogenic?

CPD p.Phe197Leu (c.591C>A) is classified Likely benign in CPD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). AlphaMissense: likely benign (0.3132); Very rare (popmax 8.74e-05%, nfe).

How common is CPD p.Phe197Leu (c.591C>A) in the general population?

CPD p.Phe197Leu (c.591C>A) is very rare (popmax 8.74e-05%, nfe) (gnomAD).

What do computational predictors say about CPD p.Phe197Leu (c.591C>A)?

AlphaMissense predicts likely benign (score 0.3132) — an in-silico prediction, not a clinical call.

CPD p.Phe197Leu

c.591C>A · VCV4656042

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3132 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.74e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3132	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -4.84	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 1.3	GERP -0.84, phastCons 0.95
Overall
CADD	5.974	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 8.74e-05% European (non-Finnish) · 1/1,144,606 alleles

Overall 7.32e-05% 1/1,365,726 alleles · very rare

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.Phe197Leu
Coding: c.591C>A
MANE Select: NM_004839 · reported on NM_001304
Type: single nucleotide variant
Location: chr17:30379571 (GRCh38)
Structure: AlphaFold pLDDT 89.20

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

Similar variants

HOMER2 p.Val197= Likely benign ★ same residue
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

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-phe197leu (accessed [today's date]).

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