Is SIN3A p.Asp7Ala (c.20A>C) pathogenic?

SIN3A p.Asp7Ala (c.20A>C) is classified Uncertain significance in SIN3A (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-22). AlphaMissense: likely benign (0.2299); Very rare (popmax 0.00401%, afr).

How common is SIN3A p.Asp7Ala (c.20A>C) in the general population?

SIN3A p.Asp7Ala (c.20A>C) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about SIN3A p.Asp7Ala (c.20A>C)?

AlphaMissense predicts likely benign (score 0.2299) — an in-silico prediction, not a clinical call.

SIN3A p.Asp7Ala

c.20A>C · VCV3392713

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2299 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2299	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -7.44	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 7.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 17 kb · p 1.7e-07 · regional, not allelic
Overall
CADD	24.7	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 0.00401% African / African-American · 3/74,874 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,612,138 alleles · very rare exomes 2/1,459,930 · genomes 1/152,208 · joint denominator

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.Asp7Ala
Coding: c.20A>C
MANE Select: NM_001145358
Type: single nucleotide variant
Location: chr15:75430356 (GRCh38)
Gene constraint: LOEUF 0.14 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 69.67
Residue 7: the 'disordered' region

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

Similar variants

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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
SIN3A p.Arg935Ter Pathogenic/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/sin3a-p-asp7ala (accessed [today's date]).

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