Is SLC19A1 p.Ala324Val (c.971C>T) pathogenic?

SLC19A1 p.Ala324Val (c.971C>T) is classified Uncertain significance in SLC19A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-22). AlphaMissense: ambiguous (0.4068); Ultra-rare (popmax 0.0469%, nfe).

How common is SLC19A1 p.Ala324Val (c.971C>T) in the general population?

SLC19A1 p.Ala324Val (c.971C>T) is ultra-rare (popmax 0.0469%, nfe) (gnomAD).

What do computational predictors say about SLC19A1 p.Ala324Val (c.971C>T)?

AlphaMissense predicts ambiguous (score 0.4068) — an in-silico prediction, not a clinical call.

SLC19A1 p.Ala324Val

c.971C>T · rs200647386 · VCV1355078

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4068 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0469%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4068	ambiguous
REVEL	0.639	indeterminate
SaProt	LLR -6.81	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP -1.9, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 22 kb · p 0.89 · regional, not allelic
Overall
CADD	23.6	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 0.0469% European (non-Finnish) · 518/1,104,708 alleles

Filtering AF 0.0435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0422%

Overall 0.0384% 557/1,452,008 alleles · ultra-rare exomes 511/1,301,354 · genomes 46/150,654 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0469%	2,133
Ashkenazi Jewishnot grpmax-eligible	0.0461%	2,170
Remaining individualsnot grpmax-eligible	0.029%	3,444
Admixed American	0.0163%	6,145
African / African-American	0.006%	16,675
Finnishnot grpmax-eligible	0.00547%	18,272

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: SLC19A1
Protein: p.Ala324Val
Coding: c.971C>T
MANE Select: NM_194255
dbSNP: rs200647386
Type: single nucleotide variant
Location: chr21:45530950 (GRCh38)
Gene constraint: LOEUF 1.585 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.30 · 19 PDB
Residue 324: a turn

Full SLC19A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SLC19A1 p.Ala324= Benign ★★ same residue
COL18A1 p.Arg1081Ter Pathogenic/Likely pathogenic ★★ same type
COL18A1 p.Arg915Ter Pathogenic/Likely pathogenic ★★ same type
RFC1 p.Arg383Ter Pathogenic/Likely pathogenic ★★ same type
COL18A1 c.*30G>A Uncertain significance ★★ same type
COL18A1 p.Ala1089Thr Uncertain significance ★★ ⚠ same type
COL18A1 p.Ala1254Val Uncertain significance ★★ ⚠ same type
COL18A1 p.Arg1081Gln Uncertain significance ★★ ⚠ 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/slc19a1-p-ala324val (accessed [today's date]).

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