Is PDS5A p.Pro1111Ser (c.3331C>T) pathogenic?

PDS5A p.Pro1111Ser (c.3331C>T) is classified Uncertain significance in PDS5A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-07). AlphaMissense: likely benign (0.1922); Very rare (popmax 0.00449%, eas); Associated with autism spectrum disorder.

What condition is associated with PDS5A p.Pro1111Ser (c.3331C>T)?

PDS5A p.Pro1111Ser (c.3331C>T) is associated with autism spectrum disorder (ClinVar).

How common is PDS5A p.Pro1111Ser (c.3331C>T) in the general population?

PDS5A p.Pro1111Ser (c.3331C>T) is very rare (popmax 0.00449%, eas) (gnomAD).

What do computational predictors say about PDS5A p.Pro1111Ser (c.3331C>T)?

AlphaMissense predicts likely benign (score 0.1922) — an in-silico prediction, not a clinical call.

PDS5A p.Pro1111Ser

c.3331C>T · VCV3778678

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1922 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00449%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autism spectrum disorder

Computational evidence

Protein change
AlphaMissense	0.1922	likely benign
REVEL	0.171	moderately benign-leaning
SaProt	LLR -7.91	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.53	unconstrained · MANE · 53 kb · p 3.1e-34 · regional, not allelic
Overall
CADD	26.7	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00449% East Asian · 2/44,530 alleles

Filtering AF 0.000744% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000279%

Overall 0.000415% 6/1,444,374 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00449%	22,265
Remaining individualsnot grpmax-eligible	0.00323%	30,975
South Asian	0.00227%	44,033

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: PDS5A
Protein: p.Pro1111Ser
Coding: c.3331C>T
MANE Select: NM_001100399
Type: single nucleotide variant
Location: chr4:39848859 (GRCh38)
Gene constraint: LOEUF 0.52 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 82.61
Residue 1111: a UniProt-annotated variant site (found in a patient with cohesinopathy; uncertain significance)

Full PDS5A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autism spectrum disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PDS5A c.654+5G>C Uncertain significance ★ same type
PDS5A p.Ala1048Asp Uncertain significance ★ ⚠ same type
PDS5A p.Ala1299Thr Uncertain significance ★ ⚠ same type
PDS5A p.Ala630Val Uncertain significance ★ same type
PDS5A p.Ala787Val Uncertain significance ★ ⚠ same type
PDS5A p.Arg1235Gln Uncertain significance ★ ⚠ same type
PDS5A p.Arg1272His Uncertain significance ★ ⚠ same type
PDS5A p.Arg255Thr 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/pds5a-p-pro1111ser (accessed [today's date]).

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