Is SIN3A p.Ala780Val (c.2339C>T) pathogenic?

SIN3A p.Ala780Val (c.2339C>T) is classified Uncertain significance in SIN3A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-29). AlphaMissense: likely benign (0.0816); Ultra-rare (popmax 0.012%, afr).

How common is SIN3A p.Ala780Val (c.2339C>T) in the general population?

SIN3A p.Ala780Val (c.2339C>T) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about SIN3A p.Ala780Val (c.2339C>T)?

AlphaMissense predicts likely benign (score 0.0816) — an in-silico prediction, not a clinical call.

SIN3A p.Ala780Val

c.2339C>T · rs369396162 · VCV1904313

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0816 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0816	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -4.99	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 8.7	GERP 0.3, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 23 kb · p 1.4e-14 · regional, not allelic
Overall
CADD	22.1	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 0.012% African / African-American · 9/75,024 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.00173% 28/1,614,002 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,336
Admixed American	0.01%	10,002
South Asian	0.00549%	18,216
Remaining individualsnot grpmax-eligible	0.0032%	31,254
Finnishnot grpmax-eligible	0.00313%	31,957
East Asian	0.00223%	44,888
European (non-Finnish)	0.000254%	393,335

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: SIN3A
Protein: p.Ala780Val
Coding: c.2339C>T
MANE Select: NM_001145358
dbSNP: rs369396162
Type: single nucleotide variant
Location: chr15:75392754 (GRCh38)
Gene constraint: LOEUF 0.14 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 69.67
Residue 780: the 'interaction with ncor1' region; the 'interaction with hdac1 and arid4b' region

Full SIN3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SIN3A p.Ala780= Benign/Likely benign ★★ same residue
SIN3A p.Arg1140Ter Pathogenic ★★ same type
SIN3A p.Arg471Ter Pathogenic ★★ same type
SIN3A p.Arg537Ter Pathogenic ★★ same type
SIN3A p.Arg553Ter Pathogenic/Likely pathogenic ★★ same type
SIN3A p.Arg559Ter Pathogenic/Likely pathogenic ★★ same type
SIN3A p.Arg718Ter Pathogenic/Likely pathogenic ★★ same type
SIN3A p.Arg897Ter 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/sin3a-p-ala780val (accessed [today's date]).

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