Is DRC7 p.Glu339Lys (c.1015G>A) pathogenic?

DRC7 p.Glu339Lys (c.1015G>A) is classified Uncertain significance in DRC7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-20). AlphaMissense: likely pathogenic (0.9487); Ultra-rare (popmax 0.0267%, eas).

How common is DRC7 p.Glu339Lys (c.1015G>A) in the general population?

DRC7 p.Glu339Lys (c.1015G>A) is ultra-rare (popmax 0.0267%, eas) (gnomAD).

What do computational predictors say about DRC7 p.Glu339Lys (c.1015G>A)?

AlphaMissense predicts likely pathogenic (score 0.9487) — an in-silico prediction, not a clinical call.

DRC7 p.Glu339Lys

c.1015G>A · rs745561928 · VCV3085744

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9487 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9487	likely pathogenic · top 4% in DRC7
REVEL	0.808	moderately pathogenic-leaning
SaProt	LLR -12.36	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 33 kb · p 0.0015 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0267% East Asian · 12/44,888 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00459% 74/1,613,386 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0267%	3,741
European (non-Finnish)	0.00492%	20,345
South Asian	0.0022%	45,541
Remaining individualsnot grpmax-eligible	0.0016%	62,468
Finnishnot grpmax-eligible	0.00158%	63,446

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: DRC7
Protein: p.Glu339Lys
Coding: c.1015G>A
MANE Select: NM_001289162
dbSNP: rs745561928
Type: single nucleotide variant
Location: chr16:57707616 (GRCh38)
Gene constraint: LOEUF 0.883 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.69 · 1 PDB

Full DRC7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRC7 p.Ala510Pro Uncertain significance ★ ⚠ same type
DRC7 p.Ala605Val Uncertain significance ★ ⚠ same type
DRC7 p.Ala629Thr Uncertain significance ★ ⚠ same type
DRC7 p.Ala65Val Uncertain significance ★ ⚠ same type
DRC7 p.Ala709Val Uncertain significance ★ ⚠ same type
DRC7 p.Ala769Val Uncertain significance ★ ⚠ same type
DRC7 p.Arg103His Uncertain significance ★ ⚠ same type
DRC7 p.Arg112His 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/drc7-p-glu339lys (accessed [today's date]).

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