Is DDX27 p.Pro705Ser (c.2113C>T) pathogenic?

DDX27 p.Pro705Ser (c.2113C>T) is classified Uncertain significance in DDX27 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-07). AlphaMissense: likely benign (0.0677); Very rare (popmax 0.000932%, nfe).

How common is DDX27 p.Pro705Ser (c.2113C>T) in the general population?

DDX27 p.Pro705Ser (c.2113C>T) is very rare (popmax 0.000932%, nfe) (gnomAD).

What do computational predictors say about DDX27 p.Pro705Ser (c.2113C>T)?

AlphaMissense predicts likely benign (score 0.0677) — an in-silico prediction, not a clinical call.

DDX27 p.Pro705Ser

c.2113C>T · rs774804993 · VCV2396776

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0677 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0677	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -9.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.92 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 17 kb · p 9e-11 · regional, not allelic
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P736S vs ClinVar P705S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000932% European (non-Finnish) · 11/1,179,980 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000682% 11/1,613,940 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: DDX27
Protein: p.Pro705Ser
Coding: c.2113C>T
MANE Select: NM_017895
dbSNP: rs774804993
Type: single nucleotide variant
Location: chr20:49242203 (GRCh38)
Gene constraint: LOEUF 0.528 · pLI 0.29 (gnomAD)
Structure: AlphaFold pLDDT 72.06
Residue 705: the 'disordered' region

Full DDX27 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDX27 p.Ala239= Benign ★★ same type
DDX27 p.Glu172Lys Benign ★★ same type
DDX27 c.52C>G Uncertain significance ★ same type
DDX27 c.-33G>A Uncertain significance ★ ⚠ same type
DDX27 p.Ala147Thr Uncertain significance ★ ⚠ same type
DDX27 p.Ala256Thr Uncertain significance ★ ⚠ same type
DDX27 p.Ala308Val Uncertain significance ★ ⚠ same type
DDX27 p.Ala553Val 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/ddx27-p-pro705ser (accessed [today's date]).

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