Is SALL1 p.Pro651= (c.1953C>T) pathogenic?

SALL1 p.Pro651= (c.1953C>T) is classified Likely benign in SALL1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). Ultra-rare (popmax 0.0118%, nfe); Associated with Townes-Brocks syndrome.

What condition is associated with SALL1 p.Pro651= (c.1953C>T)?

SALL1 p.Pro651= (c.1953C>T) is associated with Townes-Brocks syndrome, Townes-Brocks syndrome 1 (ClinVar).

How common is SALL1 p.Pro651= (c.1953C>T) in the general population?

SALL1 p.Pro651= (c.1953C>T) is ultra-rare (popmax 0.0118%, nfe) (gnomAD).

SALL1 p.Pro651=

c.1953C>T · rs147169088 · VCV1628766

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0118%, nfe)

Conditions

Townes-Brocks syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.2	GERP -2.2, phastCons 0.014
Overall
CADD	0.552	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0118% European (non-Finnish) · 139/1,180,050 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00956%

Overall 0.01% 162/1,614,014 alleles · ultra-rare exomes 153/1,461,810 · genomes 9/152,204 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0144%	6,943
European (non-Finnish)grpmax	0.0118%	8,490
Admixed American	0.01%	10,001
South Asian	0.00549%	18,217
African / African-American	0.004%	24,978

Remaining individuals 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: SALL1
Protein: p.Pro651=
Coding: c.1953C>T
MANE Select: NM_002968
dbSNP: rs147169088
Type: single nucleotide variant
Location: chr16:51140269 (GRCh38)
Gene constraint: LOEUF 0.228 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 49.54

Full SALL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Townes-Brocks syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Townes-Brocks syndrome 1

Similar variants

SALL1 p.Arg1054Ter Pathogenic/Likely pathogenic ★★ same condition
SALL1 p.Arg276Ter Pathogenic/Likely pathogenic ★★ same condition
SALL1 p.Arg786Ter Pathogenic ★★ same condition
SALL1 p.Gln201Ter Pathogenic/Likely pathogenic ★★ same condition
SALL1 p.Gln237Ter Pathogenic/Likely pathogenic ★★ same condition
SALL1 p.Gln272Ter Pathogenic ★★ same condition
SALL1 p.Gln291Ter Pathogenic/Likely pathogenic ★★ same condition
SALL1 p.Gln323Ter Pathogenic ★★ same condition

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/sall1-p-pro651 (accessed [today's date]).

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