Is OGFR p.Pro606= (c.1818G>A) pathogenic?

OGFR p.Pro606= (c.1818G>A) is classified Likely benign in OGFR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-13). Common (popmax 42.9%, eas) — too common for a highly-penetrant pathogenic allele.

OGFR p.Pro606=

Q: How common is OGFR p.Pro606= (c.1818G>A) in the general population?

OGFR p.Pro606= (c.1818G>A) is common (popmax 42.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1818G>A · VCV3302225

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 42.9%, eas) — too common for a highly-penetrant pathogenic allele

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 -5.4	GERP -0.75
Overall
CADD	5.441	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 42.9% East Asian · 12,791/29,804 alleles

Filtering AF 42.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 42%

Overall 7.19% 76,825/1,068,868 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	42.9%	2
South Asian	18.5%	5
Admixed American	16.8%	6
African / African-American	16.3%	6
Amishnot grpmax-eligible	15.4%	7
Middle Eastern	14.9%	7
Ashkenazi Jewishnot grpmax-eligible	12.4%	8
Finnishnot grpmax-eligible	11.9%	8
Remaining individualsnot grpmax-eligible	9.77%	10
European (non-Finnish)	4.02%	25

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: OGFR
Protein: p.Pro606=
Coding: c.1818G>A
MANE Select: NM_007346
Type: single nucleotide variant
Location: chr20:62813433 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.00
Residue 606: the 'disordered' region; the '7 x 20 aa approximate tandem repeats of [st]-p-s-e-t-p-g-p-[sr]-p-a-g-p-[at]-[gr]-d-e-p-a-[ek]' region

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

Similar variants

OGFR p.Ala253Val Uncertain significance ★ ⚠ same type
OGFR p.Ala411Thr Uncertain significance ★ ⚠ same type
OGFR p.Ala469Thr Uncertain significance ★ ⚠ same type
OGFR p.Ala480Val Uncertain significance ★ ⚠ same type
OGFR p.Ala627Val Uncertain significance ★ ⚠ same type
OGFR p.Ala655Thr Uncertain significance ★ ⚠ same type
OGFR p.Ala660Val Uncertain significance ★ ⚠ same type
OGFR p.Arg138Gln 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/ogfr-p-pro606 (accessed [today's date]).

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