Is PDCD6IP p.Ser770Pro (c.2308T>C) pathogenic?

PDCD6IP p.Ser770Pro (c.2308T>C) is classified Likely benign in PDCD6IP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). AlphaMissense: likely benign (0.0759); Rare (popmax 0.283%, mid).

How common is PDCD6IP p.Ser770Pro (c.2308T>C) in the general population?

PDCD6IP p.Ser770Pro (c.2308T>C) is rare (popmax 0.283%, mid) (gnomAD).

What do computational predictors say about PDCD6IP p.Ser770Pro (c.2308T>C)?

AlphaMissense predicts likely benign (score 0.0759) — an in-silico prediction, not a clinical call.

PDCD6IP p.Ser770Pro

c.2308T>C · VCV4083727

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0759 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.283%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0759	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -5.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -3
Regional constraint	o/e 0.98	unconstrained · MANE · 2,508 bp · p 0.82 · regional, not allelic
Overall
CADD	8.626	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.283% Middle Eastern · 17/6,014 alleles

Filtering AF 0.207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.196%

Overall 0.0192% 306/1,593,928 alleles · rare exomes 285/1,441,598 · genomes 21/152,330 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.283%	354
South Asian	0.233%	430
Remaining individualsnot grpmax-eligible	0.0292%	3,430
Ashkenazi Jewishnot grpmax-eligible	0.0274%	3,647
European (non-Finnish)	0.00444%	22,523
African / African-American	0.00409%	24,464
Admixed American	0.00351%	28,504
Finnishnot grpmax-eligible	0.00156%	63,898

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: PDCD6IP
Protein: p.Ser770Pro
Coding: c.2308T>C
MANE Select: NM_013374
Type: single nucleotide variant
Location: chr3:33865306 (GRCh38)
Gene constraint: LOEUF 0.583 · pLI 0.19 (gnomAD)
Structure: AlphaFold pLDDT 84.16 · 19 PDB
Residue 770: the 'interaction with eiav p9' region; the 'interaction with sdcbp' region; the 'self-association' region; the 'disordered' region

Full PDCD6IP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDCD6IP p.Ala726= Likely benign ★★ same type
PDCD6IP p.Gly429Ser Benign ★★ ⚠ same type
PDCD6IP p.Gly778Ala Benign ★★ same type
PDCD6IP p.Pro749= Benign ★★ same type
PDCD6IP p.Thr789= Benign ★★ same type
PDCD6IP p.Ala657Val Uncertain significance ★ ⚠ same type
PDCD6IP p.Ala719Thr Conflicting classifications of pathogenicity ★ ⚠ same type
PDCD6IP p.Ala726Val 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/pdcd6ip-p-ser770pro (accessed [today's date]).

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