Is PDE6A p.Phe783= (c.2349C>T) pathogenic?

PDE6A p.Phe783= (c.2349C>T) is classified Likely benign in PDE6A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-19). Ultra-rare (popmax 0.0164%, mid).

How common is PDE6A p.Phe783= (c.2349C>T) in the general population?

PDE6A p.Phe783= (c.2349C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

PDE6A p.Phe783=

c.2349C>T · rs202092523 · VCV1121503

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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 -0.36	GERP -5.6
Overall
CADD	5.884	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00322%

Overall 0.00701% 113/1,612,060 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.139%	722
Middle Easterngrpmax	0.0164%	6,080
Remaining individualsnot grpmax-eligible	0.00801%	12,481
Finnishnot grpmax-eligible	0.00625%	16,011
Admixed American	0.005%	19,995
European (non-Finnish)	0.00458%	21,819
South Asian	0.0033%	30,347
East Asian	0.00223%	44,888
African / African-American	0.00134%	74,884

Ashkenazi Jewish 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: PDE6A
Protein: p.Phe783=
Coding: c.2349C>T
MANE Select: NM_000440
dbSNP: rs202092523
Type: single nucleotide variant
Location: chr5:149866179 (GRCh38)
Gene constraint: LOEUF 0.888 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.80
Residue 783: the pdease domain

Full PDE6A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDE6A p.Phe783fs Pathogenic ★ same residue
PDE6A c.1065+2T>A Pathogenic/Likely pathogenic ★★ same type
PDE6A c.1263+1G>T Pathogenic/Likely pathogenic ★★ same type
PDE6A c.1407+1G>C Pathogenic/Likely pathogenic ★★ same type
PDE6A c.1620+1G>A Pathogenic ★★ same type
PDE6A c.1620+2T>A Pathogenic/Likely pathogenic ★★ same type
PDE6A c.1926+1G>A Pathogenic ★★ same type
PDE6A c.1927-1G>C Pathogenic/Likely pathogenic ★★ 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/pde6a-p-phe783 (accessed [today's date]).

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