Is SIN3A p.Pro279Leu (c.836C>T) pathogenic?

SIN3A p.Pro279Leu (c.836C>T) is classified Benign in SIN3A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-01). AlphaMissense: likely benign (0.0831); Rare (popmax 0.301%, nfe).

How common is SIN3A p.Pro279Leu (c.836C>T) in the general population?

SIN3A p.Pro279Leu (c.836C>T) is rare (popmax 0.301%, nfe) (gnomAD).

What do computational predictors say about SIN3A p.Pro279Leu (c.836C>T)?

AlphaMissense predicts likely benign (score 0.0831) — an in-silico prediction, not a clinical call.

SIN3A p.Pro279Leu

c.836C>T · rs61761938 · VCV717739

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0831 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.301%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0831	likely benign
REVEL	0.268	benign-leaning
SaProt	LLR -7.20	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.69 · evaluated, not missing
Constraint at this position
Conservation	phyloP 10	GERP 1.9, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 1,340 bp · p 0.042 · regional, not allelic
Overall
CADD	24.7	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 0.301% European (non-Finnish) · 3,551/1,179,974 alleles

Filtering AF 0.293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.289%

Overall 0.257% 4,148/1,614,102 alleles · rare exomes 3,889/1,461,780 · genomes 259/152,322 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.301%	332
South Asian	0.277%	361
Admixed American	0.22%	455
Remaining individualsnot grpmax-eligible	0.178%	563
Finnishnot grpmax-eligible	0.0718%	1,392
African / African-American	0.0653%	1,532
Middle Eastern	0.0165%	6,062
East Asian	0.00891%	11,222
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,802

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.Pro279Leu
Coding: c.836C>T
MANE Select: NM_001145358
dbSNP: rs61761938
Type: single nucleotide variant
Location: chr15:75411664 (GRCh38)
Gene constraint: LOEUF 0.14 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 69.67
Residue 279: the 'interaction with rest' region; the 'disordered' region

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

Similar variants

SIN3A p.Pro279= Likely benign ★★ same residue
SIN3A p.Pro279Ser Conflicting classifications of pathogenicity ★ ⚠ 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

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-pro279leu (accessed [today's date]).

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