Is DRC8 p.Phe73= (c.219C>T) pathogenic?

DRC8 p.Phe73= (c.219C>T) is classified Benign in DRC8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-08). Low-frequency (popmax 2.85%, amr).

How common is DRC8 p.Phe73= (c.219C>T) in the general population?

DRC8 p.Phe73= (c.219C>T) is low-frequency (popmax 2.85%, amr) (gnomAD).

DRC8 p.Phe73=

c.219C>T · rs142888002 · VCV770503

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.85%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.135	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.2	GERP -3.8
Overall
CADD	6.684	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.85% Admixed American · 1,712/59,968 alleles

Filtering AF 2.74% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.7%

Overall 0.421% 6,786/1,612,568 alleles · low-frequency exomes 6,151/1,460,316 · genomes 635/152,252 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	2.85%	35
European (non-Finnish)	0.388%	258
Remaining individualsnot grpmax-eligible	0.33%	303
Finnishnot grpmax-eligible	0.167%	598
South Asian	0.125%	798
Middle Eastern	0.099%	1,010
African / African-American	0.076%	1,316
East Asian	0.0134%	7,479
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,582

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: DRC8
Protein: p.Phe73=
Coding: c.219C>T
MANE Select: NM_032328
dbSNP: rs142888002
Type: single nucleotide variant
Location: chr1:245082118 (GRCh38)
Structure: AlphaFold pLDDT 65.45 · 1 PDB
Residue 73: the 'disordered' region

Full DRC8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRC8 p.Ala13Thr Uncertain significance ★ ⚠ same type
DRC8 p.Asp152Val Uncertain significance ★ same type
DRC8 p.Asp6Asn Uncertain significance ★ same type
DRC8 p.Asp6Tyr Uncertain significance ★ ⚠ same type
DRC8 p.Ile141Thr Uncertain significance ★ same type
DRC8 p.Val36Leu Uncertain significance ★ ⚠ same type
EFCAB2 p.Glu116Lys Uncertain significance ★ ⚠ same type
EFCAB2 p.Glu4Lys 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/drc8-p-phe73 (accessed [today's date]).

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