Is DMC1 p.Pro284Leu (c.851C>T) pathogenic?

DMC1 p.Pro284Leu (c.851C>T) is classified Uncertain significance in DMC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-25). AlphaMissense: likely pathogenic (0.791); Very rare (popmax 0.00223%, eas).

How common is DMC1 p.Pro284Leu (c.851C>T) in the general population?

DMC1 p.Pro284Leu (c.851C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DMC1 p.Pro284Leu (c.851C>T)?

AlphaMissense predicts likely pathogenic (score 0.791) — an in-silico prediction, not a clinical call.

DMC1 p.Pro284Leu

c.851C>T · rs2518003639 · VCV2613660

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.791 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.791	likely pathogenic
REVEL	0.478	indeterminate
SaProt	LLR -14.98	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Overall
CADD	25.6	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 0.00223% East Asian · 1/44,860 alleles

Overall 6.85e-05% 1/1,460,732 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: DMC1
Protein: p.Pro284Leu
Coding: c.851C>T
MANE Select: NM_030630 · reported on NM_007068
dbSNP: rs2518003639
Type: single nucleotide variant
Location: chr22:38521710 (GRCh38)
Structure: AlphaFold pLDDT 86.13
Residue 284: a UniProt-annotated variant site (in dee105; likely pathogenic)

Full DMC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

HID1 p.Asp201Asn Uncertain significance ★★ ⚠ same type
HID1 p.Ser87Leu Uncertain significance ★★ ⚠ same type
DMC1 p.Met200Val Benign ★★ ⚠ same type
HID1 c.1149+7C>T Benign ★★ same type
HID1 p.Gln130Glu Benign ★★ same type
HID1 p.His192Tyr Benign ★★ same type
HID1 c.1149+1G>T Likely pathogenic ★ same type
HID1 p.Arg668Ter 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/dmc1-p-pro284leu (accessed [today's date]).

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