Is SCRIB p.Ala1272= (c.3816C>T) pathogenic?

SCRIB p.Ala1272= (c.3816C>T) is classified Likely benign in SCRIB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-01). Ultra-rare (popmax 0.0281%, nfe).

How common is SCRIB p.Ala1272= (c.3816C>T) in the general population?

SCRIB p.Ala1272= (c.3816C>T) is ultra-rare (popmax 0.0281%, nfe) (gnomAD).

SCRIB p.Ala1272=

c.3816C>T · VCV3341745

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0281%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.008	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.1	GERP -2.5
Overall
CADD	1.448	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0281% European (non-Finnish) · 331/1,179,248 alleles

Filtering AF 0.0255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0245%

Overall 0.027% 435/1,611,156 alleles · ultra-rare exomes 401/1,458,866 · genomes 34/152,290 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.152%	657
Remaining individualsnot grpmax-eligible	0.0433%	2,309
European (non-Finnish)grpmax	0.0281%	3,563
African / African-American	0.0227%	4,412
Middle Eastern	0.0179%	5,590
Admixed American	0.00834%	11,991
South Asian	0.0066%	15,162
Finnishnot grpmax-eligible	0.00478%	20,910

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: SCRIB
Protein: p.Ala1272=
Coding: c.3816C>T
MANE Select: NM_182706
Type: single nucleotide variant
Location: chr8:143795068 (GRCh38)
Gene constraint: LOEUF 0.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.33 · 42 PDB

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

Similar variants

SCRIB c.3120+10C>G Benign/Likely benign ★★ same type
SCRIB c.504-9C>T Benign ★★ same type
SCRIB p.Ala1488= Likely benign ★★ same type
SCRIB p.Arg492= Benign ★★ same type
SCRIB p.Asn647= Benign/Likely benign ★★ same type
SCRIB p.Leu254= Benign ★★ same type
SCRIB p.Phe571= Benign ★★ same type
SCRIB p.Pro1343= Benign ★★ 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/scrib-p-ala1272 (accessed [today's date]).

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